Molecular and Functional Analysis of HLA-Class II Molecules Responsible for the Primary MLR in Man

Abstract

HLA-D antigen is defined as a molecule responsible for the stimulation of primary mixed lymphocyte reaction (MLR), and nineteen specificities of HLA-D have been well established in the Ninth International Histocompatibility Workshop (9th IHWS)¹. The biological and biochemical features of the HLA-D molecule have not been well understood except the fact that they stimulate primary MLR. Polymorphic cell surface glycoproteins, on the other hand, which are defined serologically on B cell are designated as HLA-DR. Fourteen alleles of HLA-DR have been established in the 9th IHWS. An HLA-D specificity shows strong correlation with a certain HLA-DR type. Furthermore, the alloantiserum against HLA-DR can inhibit the stimulation in MLR² suggesting that the DR antigen is the molecule which stimulates MLR. However, since HLA-Dw2 and Dw12, which are mutually stimulatory in MLR, are both defined as HLA-DR2 in serology, we first indicated that HLA-DR epitope is only a part of the epitopes which stimulate MLR³. Along this line, it was found that Dw4, Dw10, Dw13, Dw14, Dw15 and DKT2 were correlated with DR4. It has been suggested from these observations that HLA-D “region” consisted of at least two “loci” including HLA-DR locus. In this paper, we have clarified the molecular and functional differences of HLA-DR4 associated HLA-D specificities and of HLA-DR2 associated HLA-D specificities.