European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics最新文献

There is evidence for a link between MHC and squamous cell carcinoma of the cervix (SCCC), and different patterns of association in different patient cohorts have been reported. To investigate this subject in the Spanish population, HLA class I, -II serotypings and HLA-DQB1 oligogenotypings of 142 patients and 138 healthy sex-age-matched controls were performed. Comparative analysis of the DR2-DQ3-stratified phenotypes demonstrated a strong association between DR2 and DQ3 in SCCC (Pc9 < 7 x 10(-8)). However, no interaction was observed between the two HLA factors, which seem to confer two weak and independent risks. Thus, phenotypes with DR2 and/or DQ3 (patients, 79%, controls, 60%; P < 5 x 10(-4)) were over-represented, while the less common DR2/DQ3-negative phenotypes with the HLA class I A2 antigen were found to confer the highest risk (EF = 62%, Pc84 < 1 x 10(-2)) of SCCC. Comparative analysis of allele frequencies revealed two weakly significant increases, one for DQB1*0301 (P < 1 x 10(-2)) in low-moderate dysplasias (CINI,II), and the other for DQB1*0402 (P < 3 x 10(-2)) in severe dysplasia in situ (CINIII/CIS), and a trend for an increase of DQB1*0302 among CINIII/CIS and invasive SCCC (ISCCC). With regard to DQB1 genes encoding the DR2-associated DQ serotypes, there was no significant deviation in patients. In contrast, the frequency of DQB1*0603 was found to be weakly decreased in CINI,II (P < 5 x 10(-2)) and ISCCC (P < 3 x 10(-2)), indicating a protective effect for this DR13 serotype-associated allele. No significant association could be shown between HLA and HPV infective status. However, there is circumstantial evidence that HPV-infected lesions may have been misassigned in some cases, and the sample size was small, so a role for DQB alleles in modifying the course of HPV-induced diseases cannot be excluded. The observations in this study suggest A2, DR2, DQB1*0301, DQB1*0402 and DQB1*0603 as independent factors associated with SCCC and as relevant targets in HLA-restricted peptide presentation. Our results are consistent with the theory that HLA loci may have different contributions in susceptibility and resistance to low-moderate dysplasias, CIS and invasive SCCC.

Several recently reported HLA-DPB1 alleles have only been identified in a single family or individuals and are of unknown distribution world-wide. Many new DPB1 alleles appear to arise as a result of gene conversion-like events, which may localize variant DPB1 alleles to the population in which they were first identified. Using two SSOP-based typing methods in parallel, we have identified HLA-DPB1*6301 in an individual from rural Cameroon which has previously only been reported in a family of Mexican-American origin. The presence of DPB1*6301 was confirmed by sequence-based typing of exon 2.

At the Eleventh International HLA Histocompatibility Workshop, numerous anti-HLA class II monoclonal antibodies (mAb) were tested. For several of the polymorphic mAb, one epitope for binding has been mapped within the antigen-binding site of the class II molecules. Screening of the available bovine DRB3 and DQB exon 2 sequences revealed that some of the key amino acid (AA) motifs of these epitopes were present in cattle as well, and the question was raised whether this sharing of key AA motifs might cause interspecies cross-reactivity. Eight polymorphic anti-HLA class II mAb (seven anti-HLA DRB1 and one anti-HLA DQB) were selected for analysis of their reactivity towards bovine lymphocytes. In addition, the monomorphic anti-HLA class II mAb, 7.5.10.1, was selected for analysis, as this mAb was described to detect class II polymorphism in cattle. Flow cytometry and lymphocyte microcytotoxicity testing revealed that five of the polymorphic anti-HLA mAb were reactive with bovine lymphocytes. Furthermore, the anti-bovine reactivity of 7.5.10.1 was confirmed. These findings were supported by biochemical analysis. The anti-bovine reaction of the anti-HLA mAb did not correspond with the expected reaction, which was based on the presence of the AA, postulated to be responsible for recognition. Therefore, we suggest that the patterns of reactivity of the anti-HLA mAb are not always determined by one epitope.