Indirect recognition of donor MHC Class II antigens in human transplantation.
To investigate the role of the indirect pathway of recognition in human allograft rejection, we have mapped the dominant T cell determinant of the HLA-DRbeta1*0101 molecule presented by the DRbeta1*1101 antigen. A synthetic peptide (pp 22-35) corresponding to the sequence of the dominant peptide determinant was used for testing the frequency of in vivo activated T cells in the graft and in the periphery. DRbeta1*1101-positive patients carrying a heart allograft mismatched for the HLA-DR1 antigen showed no reactivity to pp 22-35 during quiescence. However, interleukin-2-responsive T cells, which were pp 22-35 specific, were found in the circulation prior to and at the time of acute and chronic rejection. The response of in vivo and in vitro activated T cells was inhibited at high concentrations of peptide 22-35. This data suggests that indirect recognition plays an important role in allograft rejection and that it can be abolished by high zone tolerance induction.
Liu
Z
Z
College of Physicians and Surgeons of Columbia University, Department of Pathology, New York, New York 10032, USA.
Harris
P E
PE
Colovai
A I
AI
Reed
E F
EF
Maffei
A
A
Suciu-Foca
N
N
D000208:Acute Disease; D000595:Amino Acid Sequence; D002908:Chronic Disease; D018604:Epitope Mapping; D006084:Graft Rejection / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D059810:HLA-DR Serological Subtypes; D015798:HLA-DR1 Antigen / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007108:Immune Tolerance; D016056:Immunodominant Epitopes; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015798:HLA-DR1 Antigen; C080766:HLA-DR11 antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments