The relative distribution of B35 alleles and their IEF isotypes in a HLA‐B35‐positive population

Abstract

The HLA-B35 serotype represents a group of antigens detectable by IEF, cytotoxic T cells, and by sequencing analysis. Four isotypes and eight alleles have been thus far reported. We have determined the relative frequencies of these B35 subtypes in a group of 203 unrelated people. Dot blot hybridization of PCR amplified products was performed using 23 sequence-specific oligo probes designed based on the EMBL HLA class I sequence database. The amplification was achieved by a pair of group-specific primers, producing approximately 600 bp fragments. By hybridization pattern analysis, we found that four alleles represent over 95% of the B35+ population, with relative frequency of 48.2% for B*3501, 23.7% for B*3502, 15.2% for B*3503, and 8.0% for B*3508. We also identified 3 individuals with B*3504 and one with B*3505, and seven samples with new patterns. B*3501 and B*3503 exactly correlated with the most common isotype B35.3, B*3502 and B*3504 with B35.2, B*3508 may be the B35.1 IEF isotype. The B*3505 was identified from an individual with B35 IEF variant form. Our study shows that the B35 antigen has a wide distribution of alleles, and that many more B35-related alleles may yet to be uncovered.

A structural voyage toward an understanding of the MHC‐I‐restricted immune response: lessons learned and much to be learned

“…The highly polymorphic HLA‐B35 family, with around 100 members, is found widespread throughout the human population. Within this family, the four most abundant alleles are HLA‐B*35:01 (48.2%), HLA‐B*35:02 (23.7%), HLA‐B*35:03 (15.2%), and HLA‐B*35:08 (8%) . We have investigated the HLA‐B*35:01 and HLA‐B*35:08 allomorphs, which differ by a single residue at position 156 (leucine → arginine), which is located on the α2‐helix, buried within the antigen‐binding cleft.…”

A Human CTL Recognizes a Caspase-8-Derived Peptide on Autologous HLA-B*3503 Molecules and Two Unrelated Peptides on Allogeneic HLA-B*3501 Molecules

“…COS-7 cells were grown in DMEM (Life Technologies). Cell lines BB49-EBV, LG-2-EBV, and the .221 cell lines transfected with HLA-B*3501 or HLA-B*3503 were grown in Iscove's medium (10,11). CTL clone 121 was maintained by weekly restimulation of 5 ϫ 10 5 CTL with 10 5 irradiated BB49-SC-CHN.B7 cells (BB49-SCCHN transfected with B7), pretreated for 72 h with 100 U/ml of IFN-␥, in 2 ml of Iscove's medium containing 10% human serum, 50 U/ml of IL-2, 0.8 ϫ 10 6 irradiated LG-2-EBV cells, and 1.5 ϫ 10 6 allogeneic irradiated PBMC.…”

Motif of HLA-B*3503 peptide ligands

“…It is also associated with a higher risk for several autoimmune diseases (Tiwari and Terasaki 1985). To date, ten subtypes of HLA-B35, varying by 1-3 amino acids, have been described (Bodmer et al 1995); four of them (B'3501, B'3502, B'3503, B'3508) represent about 95% of B35 molecules in the population (Ragupathi et al 1995). Strong differences in peptide binding preferences among these subtypes, as shown here for HLA-B*3501 and HLA-B*3503, demonstrates that molecular subtyping of HLA-B35 molecules is essential for evaluating disease associations or alloresponses in the transplantation setting.…”