Sequence Polymorphism of HLA-DR Beta 1 Alleles Relating to T Cell-Recognized Determinants

摘要

HLA class II molecules are a highly polymorphic family of dimeric cell surface proteins primarily involved in regulating T cell responses to extrinsic antigens. To define regions of class II molecules involved in T cell recognition, we have compared sequences of three HLA-DR Beta cDNA clones obtained from cells that all express the same serologically defined determinants but differ in terms of T cell-recognized specificities. The comparisons indicate that very few (one to four) nucleotides differ between what are almost certainly alleles of the DR Beta 1 Locus. All differences were in the first domain of the molecule and all localized to a region from amino acids 71-86. Since all differences were found only in this region of the molecules, and since DR alpha chains seem to be relatively nonpolymorphic, these positions in the DR Beta chain must play a major role in influencing T cell recognition of the DR molecule. Serological and molecular cloning experiments have shown that there are three families of class II molecules within the HLA complex, termed DP, DQ, and DR. For the DR4-DRw53 haplotype which we have studied, within the DR family, one alpha and three complete beta genes are known; one Beta gene is a pseudogene. At least two DR alpha Beta dimers are expressed.