CORECOGNITION OF HLA-A1 AND HLA-DPW3 BY A HUMAN CD4+ ALLOREACTIVE LYMPHOCYTE-T CLONE

We have generated an alloreactive proliferative T cell clone that only is stimulated by HLADPw3+ antigen presenting cells (APC) that at the same time carry HLAA1. The T cell clone is CD4+, and the proliferation is blocked by anti-DP monoclonal antibodies and not by antibodies towards other class II or towards class I molecules. Family studies show that APC with A1 and DPw3 on different haplotypes (trans) are able to stimulate the clone, and an HLA recombinant family gives evidence that the class I-carrying part of the haplotype is necessary for stimulation to occur. Stimulation is also observed with mixtures of APC expressing DPw3 and APC expressing Al, and likewise, DPw3+ APC become stimulatory when preincubated with supernatants from Al-positive cells. Our studies suggest that major histocompatibility complex (MHC) class I peptides presented by class II are allostimulatory and that APC can process MHC molecules that presumably are presented as allele-specific peptides in the context of other MHC molecules. We hypothesize that presentation ofMHC peptides by MHC molecules constitutes an important part of alloreactive phenomena in vivo and in vitro. © 1990, Rockefeller University Press., All rights reserved.