Distribution of HLA antigens in idiopathic pulmonary fibrosis

Divergent observations suggest that genetic factors contribute to the susceptibility to or clinical course of idiopathic pulmonary fibrosis. To determine whether there is an association between the major histocompatibility (HLA) system and idiopathic pulmonary fibrosis, the distribution of 35 antigens of HLA loci A and B was determined among 33 white patients with idiopathic pulmonary fibrosis and 329 healthy white control subjects. Although certain antigens tended to be more prevalent among patients with idiopathic pulmonary fibrosis compared with control subjects, there were no significant differences in the phenotype frequencies of the HLA-A and HLA-B antigens between these 2 groups. Thus, although subtle associations may exist between the HLA loci and idiopathic pulmonary fibrosis, these results indicate that antigens of the HLA-A and HLA-B loci are not linked with major risk factors in this disease.     

Unusually high frequency of Epstein-Barr virus genetic variants in Papua New Guinea that can escape cytotoxic T-cell recognition: implications for virus evolution

Cytotoxic T lymphocytes (CTLs) which recognize viral antigens in association with human leukocyte antigens (HLAs) play an important role in controlling persistent virus infections. These viruses use several mechanisms to evade the immune response, including mutations that affect either T-cell receptor recognition or binding of viral epitopes to the HLA. It has recently been proposed that the distribution of HLA frequencies and the specific CTL response may influence the long-term evolution of Epstein-Barr virus (EBV) by selecting variants which lack immunodominant CTL epitopes. To test this hypothesis, we have studied EBV isolates from two genetically distinct Papua New Guinea (PNG) populations, residing in coastal and highland regions, for polymorphism within seven viral CTL epitope sequences restricted through several class I HLAs. Surprisingly, all EBV isolates analyzed displayed identical amino acid substitutions within HLA A11-, B35- and B8-restricted CTL epitope sequences which completely abrogated CTL recognition and binding of synthetic peptides to HLA molecules. Furthermore, these substitutions revealed no correlation with the contemporary distribution of HLAs in the different PNG populations, which argues for a minimal influence of immune pressure. The sequence homology between EBV isolates from coastal and highland PNG suggests that the virus may have had a single origin and, more importantly, that these isolates are genetically distinct from those present in a Caucasian population.     

Analysis of restriction fragment length polymorphism for the HLA-DR gene in Japanese patients with sarcoidosis

BACKGROUND: It is commonly assumed that some immunological disorder may play a part in the pathogenesis of sarcoidosis. Previous studies by several groups have shown a significant association with HLA-DR antigens in patients with sarcoidosis. In this study, restriction fragment length polymorphism (RFLP) analysis of the HLA-DR gene was designed to confirm the association at the gene level and to look for a gene rearrangement which may influence susceptibility to sarcoidosis. METHODS: Thirty two unrelated Japanese patients with sarcoidosis were tested for HLA antigens and subjected to RFLP analysis after digestion with Eco RI, Pst I, Bam HI, Pvu II, and Hind III by using an HLA-DR beta cDNA probe. A group of 47 unrelated healthy Japanese subjects served as controls. Frequencies of each restriction fragment were compared between the patients and the control subjects. Correlation between fragment frequencies and clinical features were also analysed. RESULTS: No restriction fragments of HLA-DR beta gene were found specific to the patients with sarcoidosis. The RFLP analysis could detect polymorphism of HLA-DR beta genes that was not distinguishable by conventional serological methods. Several restriction fragments of the DR beta gene were seen only in DRw52 positive individuals, and showed higher frequencies in the patients than in control subjects. The patients with these DNA fragments were likely to have limited stage disease with no ophthalmic involvement. CONCLUSIONS: An association between HLA and sarcoidosis was noted at the DNA level, although no restriction fragments were specific for this disease. RFLP analysis of the HLA gene is a more useful method than the usual HLA typing, and should be the first step in identifying the gene sequence which is connected with susceptibility to sarcoidosis.     

Is there an immunogenetic basis for Peyronie's disease?

PURPOSE: Despite numerous studies, there has been no definitive HLA association with Peyronie's disease. Results of available studies have been reviewed and compared to determine if the cumulative evidence supports any immunogenetic, HLA association with Peyronie's disease. MATERIALS AND METHODS: Data from reports of HLA associations with Peyronie's disease were reanalyzed by categories of reported HLA class I or class II antigens in comparison with recently available large population analysis of the frequencies of these antigens in the normal population. Data were also considered by whether they were derived from population or family analyses. RESULTS: The results of 4 series of patients testing an association of Peyronie's disease with the HLA class I antigens, in particular the B7 related antigens, were contradictory. A B7 association was not confirmed in 2 larger series and, in fact, the B7 related antigens were observed in frequencies expected in a normal population, suggesting that the associations observed in the smaller series were due to chance. An association with the HLA class II antigen, DQ2, was found in 1 of the larger series. Reported family studies suggest a genetic basis for Peyronie's disease but do not indicate a gene closely linked to the HLA complex. CONCLUSIONS: Considering all available data, Peyronie's disease appears to be multifactorial in pathogenesis. Because Peyronie's disease is likely heterogeneous and because available studies have analyzed serologically defined HLA antigens, future studies to define HLA alleles molecularly and to characterize patient subgroups may clarify an immunogenetic basis.     

Identification of T-cell epitopes on the Rhesus polypeptides in autoimmune hemolytic anemia

We have shown previously that the Rhesus (Rh) polypeptides are the commonest targets for pathogenic anti-red blood cell (RBC) autoantibodies in patients with autoimmune hemolytic anemia (AIHA). The aim of the current work was to determine whether activated T cells from such patients also mount recall responses to epitopes on these proteins. Two panels of overlapping 15-mer peptides, corresponding to the sequences of the 30-kD Rh proteins associated with expression of the D and Cc/Ee blood group antigens, were synthesized and screened for the ability to stimulate the in vitro proliferation of mononuclear cells from the peripheral blood or spleen of nine AIHA cases. Culture conditions were chosen that favor recall proliferation by previously activated T cells, rather than primary responses. In seven of the patients, including all four cases with autoantibody to the Rh proteins, two or more peptides elicited proliferation, but cells from eight of nine patients with other anemias and seven of nine healthy donors failed to respond to the panels. Multiple peptides were also stimulatory in two positive control donors who had been alloimmunized with Rh D-positive RBCs. Six different profiles of peptides elicited responses in the AIHA patients, and this variation may reflect the different HLA types in the group. Stimulatory peptides were identified throughout domains shared between, or specific to, each of the related 30-kD Rh proteins, but T cells that responded to nonconserved regions did not cross-react with the alternative sequences. Anti-major histocompatibility complex class II antibodies blocked the responses and depletion experiments confirmed that the proliferating mononuclear cells were T cells. Notably, splenic T cells that proliferated against multiple Rh peptides also responded to intact RBCs. We propose that pathogenic autoantibody production in many cases of AIHA is driven by the activation of T-helper cells specific for previously cryptic epitopes on the Rh proteins.     

Cross-reactive memory T cells for Epstein-Barr virus augment the alloresponse to common human leukocyte antigens: degenerate recognition of major histocompatibility complex-bound peptide by T cells and its role in alloreactivity

In the present report, cytotoxic T lymphocyte (CTL) clones are described that display dual specificity for one of two common human leukocyte antigens (HLA B14 or B35) as alloantigens, and an immunodominant epitope (FLRGRAYGL) from Epstein-Barr virus (EBV) that binds to HLA B8. These T cell clonotypes were isolated from several unrelated HLA B8+, EBV-exposed individuals, and each distinct cross-reactivity pattern was associated with a common, public T cell receptor (TCR). In some individuals, CTL cross-reactive with these alloantigens completely dominated the memory response to this EBV epitope. Moreover, these memory T cells to EBV could be reactivated as a significant component of the repertoire of CTL responding to allogeneic stimulator cells expressing either HLA B14 or B35. These data illustrate how a history of infection with an immunogenic virus such as EBV can augment responsiveness to particular alloantigens; such influences may underlie the observed clinical association between herpesvirus infection and both allograft rejection and graft-versus-host disease. We have also explored the molecular basis for T cell cross-reactivity with alloantigens using the HLA B35 allo-reactive CTL clonotype. To elucidate the structural features of peptides that may be cross-recognized by these T cells, mono-substituted analogs of the viral epitope were screened for recognition, revealing broad specificity for major histocompatibility complex (MHC)-bound peptide. Based on the particular amino acid changes tolerated by the CTL at each peptide position, the human protein sequence database was searched for possible sequences that were recognized in association with HLA B35. Four peptides were identified (MPEATVYGL, IPIAPVYGM, KPSPPYFGL, and KPIVVLHGY) that were powerful activating ligands for the CTL when presented on HLA B35 but not B8. Thus, equivalent epitopes, capable of fully activating a single TCR, were formed by peptides with minimal obvious sequence homology bound to either HLA B8 or B35. These data indicate that degenerate peptide recognition by TCR may play an important role in the vigorous response of self-MHC-restricted T cells to alloantigens.     

HLA-DRB1*08 influences the development of disease in Mexican Mestizo with spondyloarthropathy

OBJECTIVE: HLA class II encoded factors may influence the phenotype of ankylosing spondylitis (AS). These include HLA DRB1*07 for peripheral arthritis, and polymorphism of the HLA-linked LMP2 locus and HLA DRB1*08 for acute anterior uveitis (AAU). We studied the relationship between DRB1*08 and disease phenotype in additional populations of individuals with AS. METHODS: The patient population included 385 unrelated HLA-B27 positive individuals with AS. These included 204 Caucasians and 2 populations of Mexican Mestizo with AS: 106 with predominately adult onset disease from Guadalajara and 75 with predominately juvenile onset disease from Mexico City. The control population of 428 individuals included 210 random and 36 HLA-B27 positive unrelated Canadian Caucasians and 173 random and 9 HLA-B27 positive Mexican Mestizo from Mexico City. DRB1*08 typing was by sequence specific polymerase chain reaction. RESULTS: A significantly higher prevalence of DRB1*08 was observed in Mexican patients with juvenile onset disease (44.9%) and especially those with undifferentiated spondyloarthropathy (55.6%) compared to normal unrelated Mexican Mestizo (25.4%) (p < 0.01 for both) and in patients with undifferentiated spondyloarthropathy versus B27 controls (11.1%) (p = 0.03), although no significant differences were observed in within patient group comparisons based on phenotypic features of disease such as AAU and age at onset. No significant relationship between DRB1*08 and disease phenotype was evident in Caucasian individuals. CONCLUSION: Our data suggest DRB1*08 may influence the phenotype of spondyloarthritis in Mexican Mestizo, but do not support the view that DRB1*08 influences the development of AAU, as reported in a Japanese population.     

Gender differences in general practice consultations: methodological challenges in epidemiological research

The present study is an analysis of the frequencies of HFE mutations in patients with different forms of iron overload compared with the frequencies found in healthy subjects from the same region. The frequencies of HLA-A and -B antigens and HLA haplotypes were also analyzed in the same subjects. The study population included: 71 healthy individuals; 39 genetically and clinically well-characterized patients with genetic hemochromatosis (HH); and 25 patients with non-classical forms of iron overload (NCH), excluding secondary hemochromatosis. All subjects were HLA-typed and HFE-genotyped by the oligonucleotide ligation assay (OLA). The gene frequencies found for the C282Y and H63D mutations of HFE were respectively: 0.03 and 0.23 in healthy individuals, 0.86 and 0.04 in HH patients, and 0.08 and 0.48 in NCH patients. An expected significant association between HH and HLA-A3 was observed, which was found to be in linkage disequilibrium with the C282Y mutation. A new association was seen, however, between HLA-A29 and NCH, in linkage disequilibrium with the H63D mutation. Again as expected, the HLA-B antigen B7 was associated with HH in linkage disequilibrium with HLA-A3. In addition, the HLA-B antigen B44 was found to be associated with NCH but not in linkage disequilibrium with either A29 or the H63D mutation. In conclusion, a new association of the HFE H63D mutation with forms of hemochromatosis other than HH and a new association between the HLA phenotype A29 and the HFE H63D mutation were found in the same patients. These findings reinforce evidence for the involvement of the major histocompatibility class I in iron metabolism, supporting the notion of a physiological role for the immunological system in the regulation of iron load.     

On T-cell recognition of nickel as a hapten

T-cells recognize antigens as peptides associated with self-molecules encoded by genes of the HLA region. In patients with contact allergy to nickel, T-cells that are specific for non-peptide haptens have been described. Previously, we have isolated HLA class II-restricted nickel-specific T-cell clones from patients with nickel sensitivity. In this paper, data on the fine specificity of a nickel-specific HLA-DR4-restricted clone have been reevaluated. Genomic tissue typing employing polymerase chain reaction and sequence-specific primers were used. Nickel was presented to the T-cell clone by all three subtypes of HLA-DR4 included in our panel. Two different DRB4*0404-positive cells presented nickel, whereas only 3 of the 7 DRB1*0401-positive and one of the 3 DRB1*0408-positive cells restimulated the T-cell clone. These findings are compatible with the notion that nickel interacts with endogenous peptides in the antigen-presenting groove of the HLA molecule, thereby changing these peptides' antigenicity rather than their ability to bind to the HLA molecule. Variations of the endogenous peptide in the antigen-presenting groove as well as differences of the HLA molecules give the DR4 specificity of the nickel-specific clone MCE2.     

Immunogenic human leukocyte antigen class II antigens on human cardiac valves induce specific alloantibodies

BACKGROUND: The kinetics of panel reactive antibodies (PRA) and incidence of antibodies directed against human leukocyte antigen (HLA) class II were studied in patients who received a cryopreserved cardiac valve allograft. METHODS: A complement-dependent microlymphocytotoxicity test was used to determine the percentage of panel reactive antibodies. Anti-HLA class II antibodies were measured by two-color fluorescence assays. RESULTS: The panel reactive antibodies became positive in 25 (78%) of 32 recipients between 1 and 16 months after implantation. Antibodies against HLA class II antigens were detected in 11 (37%) of 30 patients. In 9 (82%) of 11 cases these antibodies were donor specific. The induction of antibodies against donor HLA class II antigens suggests that intact HLA class II antigens are expressed by viable cells within the graft. Dithiothreitol analysis showed that the antibodies were of the immunoglobulin G type. Apparently, the HLA class II antigens are expressed in an immunogenic way, as activation of specific T-helper cells is essential for the switch from immunoglobulin M to immunoglobulin G antibodies. CONCLUSIONS: Allogeneic valve transplantation is associated with the production of donor-specific anti-HLA class I and II antibodies that could contribute to graft failure. This possibly detrimental effect might be prevented by cross matching in sensitized patients.     

The HLA class I-CML association revisited taking into account the two forms of gene fusion in the Philadelphia chromosome. A multicenter study

CML patients possess either a b3-a2 or a b2-a2 fusion between the BCR and ABL genes. Depending on the type of fusion, two different series of non-self potentially immunogenic peptides may be produced. If they are presented by HLA class I molecules and recognized by cytotoxic CD8 lymphocytes, individuals could be more susceptible or resistant to leukemic cells bearing one or the other form of fusion according to their HLA class I phenotype. To test this point, the frequencies of HLA-A and HLA-B alleles were compared between b3-a2 and the b2-a2 CML patients. In essence, no difference was found whose significance could withstand correction for multiple comparisons.     

HLA types, blood groups, serum protein and red cell enzyme types among Samoans in New Zealand

101 Samoans living in New Zealand, of whom 77 had no known non-Samoan ancestry, have been typed for nine blood group systems, four serum protein and 23 red cell enzyme systems, for haemoglobin variants and antigens at the HLA A nad B loci. The frequencies of genes in these various systems suggest that Samoans fall partly into an island Melanesian-Micronesian pattern, and partly are unique. Their uniqueness is most distinctive for the HLA system.     

HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry

BACKGROUND: As of May 1, 1995, the National Marrow Donor Program had a donor registry consisting of over 1.35 million HLA-typed volunteers recruited from most major cities and states in the United States. This registry represents the largest single HLA-typed pool of normal individuals in the world. METHODS: We analyzed the HLA-A, -B, -DR locus phenotypes of the National Marrow Donor Program donors in order to estimate gene and haplotype frequencies for major racial groups of the United States: Caucasian American, Asian American, African American, Latin American, and Native American. The large size of the database allowed us to calculate the frequencies of relatively rare antigens and haplotypes with more accuracy than previous studies. RESULTS: We observed 89,522 distinguishable HLA-A, -B phenotypes in 1,351,260 HLA-A, -B-typed donors and 302,867 distinguishable HLA-A, -B, -DR phenotypes in 406,503 HLA-A, -B, -DR-typed donors. Gene and haplotype frequencies differed remarkably among the five racial groups, with African Americans and Asian Americans having a large number of haplotypes that were specific to their racial groups, whereas Caucasian Americans, Latin Americans, and Native Americans shared a number of common haplotypes. CONCLUSIONS: These data represent an important resource for investigators in the fields of transplantation and population genetics. The gene and haplotype frequencies can be used to aid clinicians in advising patients about the probability of finding a match within a specific ethnic group, or to determine donor recruitment goals and strategies. The information is also a valuable resource for individuals who are interested in population genetics, selection and evolution of polymorphic human genes, and HLA-disease association.     

HLA, Gm, and Km polymorphisms and immunity to infectious diseases in South Amerinds

Isolated South Amerinds, a population at very high risk from infectious disease, mount good immune responses to pneumococcal polysaccharides, viral antigens and other immunogens. No unusual immunoglobulin allotype or HLA antigen, which might explain the high risk from infectious disease, was found among them. Responses are examined in relation to the immunogenetic markers that are most prevalent. Amerinds with Gm 1,2,17,21 responded less well than persons without this haplotype to 10 of 12 pneumococcal polysaccharides, and those who were homozygous at the HLA class I loci responded less well to viral antigens. However, these differences are not strong and there are few such findings relative to the number of possibilities examined. The most distinctive immunogenetic characteristic of these populations is their low level of polymorphism at all tested loci. Their susceptibility to infectious agents can be attributed to this genetic uniformity and a consequent ability of pathogens to adapt to the population.     

HLA genes in patients with pulmonary tuberculosis in the Kirghiz population]

The immunogenetic features of the HLA system were studied in 116 Kirghiz patients with pulmonary tuberculosis and 120 apparently healthy individuals of the same nationality (a control group). HLA antigen typing was made by the routine microlymphocytotoxic test. The antigens Bw53, Bw62(15), DR2 and DR7 which should be regarded as markers of the disease were more commonly found in the HLA phenotype in Kirghiz patients with tuberculosis than in healthy individuals. The risk for tuberculosis increased in carriers having HLA haplotypes with the DR allele.     

Identification of a yeast artificial chromosome clone encoding an accessory factor for the human interferon gamma receptor: evidence for multiple accessory factors

Human chromosomes 6 and 21 are both necessary to confer sensitivity to human interferon gamma (Hu-IFN-gamma), as measured by the induction of human HLA class I antigen. Human chromosome 6 encodes the receptor for Hu-IFN-gamma, and human chromosome 21 encodes accessory factors for generating biological activity through the Hu-IFN-gamma receptor. A small region of human chromosome 21 that is responsible for encoding such factors was localized with hamster-human somatic cell hybrids carrying an irradiation-reduced fragment of human chromosome 21. The cell line with the minimum chromosome 21-specific DNA is Chinese hamster ovary 3x1S. To localize the genes further, 10 different yeast artificial chromosome clones from six different loci in the vicinity of the 3x1S region were fused to a human-hamster hybrid cell line (designated 16-9) that contains human chromosome 6q (supplying the Hu-IFN-gamma receptor) and the human HLA-B7 gene. These transformed 16-9 cells were assayed for induction of class I HLA antigens upon treatment with Hu-IFN-gamma. Here we report that a 540-kb yeast artificial chromosome encodes the necessary species-specific factor(s) and can substitute for human chromosome 21 to reconstitute the Hu-IFN-gamma-receptor-mediated induction of class I HLA antigens. However, the factor encoded on the yeast artificial chromosome does not confer antiviral protection against encephalomyocarditis virus, demonstrating that an additional factor encoded on human chromosome 21 is required for the antiviral activity.     

Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion

We use population genetics theory and computer simulations to demonstrate that population bottlenecks cause a characteristic mode-shift distortion in the distribution of allele frequencies at selectively neutral loci. Bottlenecks cause alleles at low frequency (< 0.1) to become less abundant than alleles in one or more intermediate allele frequency class (e.g., 0.1-0.2). This distortion is transient and likely to be detectable for only a few dozen generations. Consequently only recent bottlenecks are likely to be detected by tests for distortions in distributions of allele frequencies. We illustrate and evaluate a qualitative graphical method for detecting a bottleneck-induced distortion of allele frequency distributions. The simple novel method requires no information on historical population sizes or levels of genetic variation; it requires only samples of 5 to 20 polymorphic loci and approximately 30 individuals. The graphical method often differentiates between empirical datasets from bottlenecked and nonbottlenecked natural populations. Computer simulations show that the graphical method is likely (P > .80) to detect an allele frequency distortion after a bottleneck of < or = 20 breeding individuals when 8 to 10 polymorphic microsatellite loci are analyzed.     

Liver histology in chronic hemodialysis patients infected with hepatitis C virus

To investigate the influence of genetic and/or environmental factors in the development and shaping of the human peripheral T cell repertoire the authors studied the T-cell receptor (TCR) V beta usage in 10 adult monozygous (Mz) and nine dizygous (Dz) twin pairs living in a Plasmodium falciparum endemic area in West Africa. The TCR repertoire was determined using a small panel of anti-V beta specific monoclonal antibodies (MoAbs) using conventional immunofluorescence assays. The results revealed that the V beta repertoire was similar to that recently described for a Caucasian population using a similar panel of antibodies. The frequencies of particular V beta genes tested were influenced neither by anti-malarial antibody titres nor by parasite densities, indicating that the P. falciparum parasite is not a dominating factor in determining the peripheral T cell repertoire. All donors were human leucocyte antigen (HLA) class I and II typed; no association was found between the expression of any V beta genes and MHC haplotype. The V beta usage was more concordant within the Mz than within the Dz pairs. For a group comprising four HLA class II identical individuals, the average within-pair difference was significantly greater than for the whole Mz group, but similar to that seen for the total Dz group. Thus, the data suggest that genetic, rather than environmental, factors have a profound effect on the shaping of the human circulating T cell repertoire and that the major genetic factors are encoded by non-HLA class II genes.     

The memory cytotoxic T-lymphocyte (CTL) response to human cytomegalovirus infection contains individual peptide-specific CTL clones that have undergone extensive expansion in vivo

Human cytomegalovirus (HCMV)-specific CD8(+) cytotoxic T lymphocytes (CTL) appear to play an important role in the control of virus replication and in protection against HCMV-related disease. We have previously reported high frequencies of memory CTL precursors (CTLp) specific to the HCMV tegument protein pp65 in the peripheral blood of healthy virus carriers. In some individuals, the CTL response to this protein is focused on only a single epitope, whereas in other virus carriers CTL recognized multiple epitopes which we identified by using synthetic peptides. We have analyzed the clonal composition of the memory CTL response to four of these pp65 epitopes by sequencing the T-cell receptors (TCR) of multiple independently derived epitope-specific CTL clones, which were derived by formal single-cell cloning or from clonal CTL microcultures. In all cases, we have observed a high degree of clonal focusing: the majority of CTL clones specific to a defined pp65 peptide from any one virus carrier use only one or two different TCRs at the level of the nucleotide sequence. Among virus carriers who have the same major histocompatibility complex (MHC) class I allele, we observed that CTL from different donors that recognize the same peptide-MHC complex often used the same Vbeta segment, although other TCR gene segments and CDR3 length were not in general conserved. We have also examined the clonal composition of CTL specific to pp65 peptides in asymptomatic human immunodeficiency virus-infected individuals. We have observed a similarly focused peptide-specific CTL response. Thus, the large population of circulating HCMV peptide-specific memory CTLp in virus carriers in fact contains individual CTL clones that have undergone extensive clonal expansion in vivo.     

Antigen presenting phenotype of Hodgkin Reed-Sternberg cells: analysis of the HLA class I processing pathway and the effects of interleukin-10 on epstein-barr virus-specific cytotoxic T-cell recognition

Approximately 40% of Hodgkin's disease (HD) cases in Western countries carry Epstein-Barr virus (EBV) in the malignant Hodgkin-Reed-Sternberg (H-RS) cells. HLA class I-restricted cytotoxic T lymphocytes (CTLs) with specificity for viral antigens expressed in H-RS cells therefore have therapeutic potential. However, a prerequisite for CTL therapy is that the tumor target be capable of processing and presenting endogenously expressed antigens via the transporter associated with antigen processing (TAP)-dependent HLA class I pathway. We have assessed the antigen-presenting phenotype of H-RS cells in two ways. First, immunohistochemical analysis of 38 HD biopsies showed that H-RS cells were uniformly TAP1/TAP2-positive and expressed HLA class I in the majority (18 of 24, 75%) of EBV-positive cases compared with only 4 of 14 (29%) of EBV-negative cases. Second, using a panel of 5 H-RS cell lines, we showed that 4 of 5 could process and present EBV proteins to HLA class I-restricted EBV-specific CTL clones. Others have reported that human interleukin-10 (IL-10), which is expressed by H-RS cells in the majority of EBV-positive HD cases, can abrogate CTL recognition in some circumstances. However, IL-10 pretreatment of the H-RS lines or of the EBV-specific CTLs had no such effect in this system. These results support the possibility that EBV-specific CTLs may be used to treat virus-positive HD.