We have generated an alloreactive proliferative T cell clone that only is stimulated by HLA-DPw3+ antigen presenting cells (APC) that at the same time carry HLA-A1. 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 A1, and likewise, DPw3+ APC become stimulatory when preincubated with supernatants from A1-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 of MHC peptides by MHC molecules constitutes an important part of alloreactive phenomena in vivo and in vitro.

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