AbstractLEW (RTI1) recipients of DA (RTIavl) skin and kidney allografts were tested for the capacity of their T lymphocytes to proliferate to three 22–24‐amino acid peptides from the hypervariable regions of the RTI‐Aavlclassical MHC class I molecule. Ten days after rejecting second‐set DA kidneyallografts, spleen cells (but interestingly not lymph node cells) from LEW recipients showed strong, LEW antigen‐presenting cell‐dependent, CD4+Tcell proliferation to peptide 1 (from the α helical region of the α1 domain). CD8+T cells showed no response to peptide 1. There was no response by the spleen cells to peptide 2 (from the β sheet of the α2 domain) or peptide 3 (from the α helical region of the α2 domain). Immunization of LEW rats with pure RTI‐Aavlclass I H chain in Freund's adjuvant gave responses identical to that seen after grafting,i.e.good CD4+T cell proliferation to peptide 1, but none to peptides 2 and 3. However, immunization of LEW rats with peptides 1, 2 and 3 in Freund's adjuvant resulted in good CD4+T cell proliferation responses to each of the peptides. These data demonstrate that indirect allorecognition can be stimulated by allograft rejection, and emphasize that the physiological processing of donor antigens will influence which peptides will be important in indirect allorecognition
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