AUTOANTIBODIES TO T-CELL RECEPTOR-BETA CHAINS IN HUMAN HEART-TRANSPLANTATION - EPITOPE AND SPECTROTYPE ANALYSES AND KINETICS OF RESPONSE

Autoantibodies against T-cell receptors have been found in two alloimm unization situations in humans: renal transplantation and pregnancy. W e carried out longitudinal studies of human heart transplant recipient s monitoring their autoantibody production to a recombinant single cha in T-cell receptor V alpha/V beta construct, a set of nested, overlapp ing peptides duplicating the complete covalent structure of an individ ual T-cell receptor beta chain and a set of peptides duplicating the f irst complementarity determining segments of 24 distinct human V beta gene products in order to define the time course, epitope specificity and recognition heterogeneity of the response. Autoantibodies against intact and peptide-defined V beta and C beta determinants were generat ed following human heart allotransplantation. The responses generally show an increase following transplantation that subsequently decreases with time, a result which is consistent with a single immunization. H owever, some patients showed elevated responses as long as 12 months f ollowing the transplant. Autoantibody anti-CDR1 spectrotype analyses d etected individual differences among patients, but 5 of 8 patients cha racterized in detail showed elevated IgG binding to CDR1 peptide epito pes of V beta 6.1, 21.1 and 22.1 gene products. Autoantibodies to CDR1 epitopes of V beta 7.1 and 8.1 were high pretransplant and remained h igh, although the relative increases with respect to the pretransplant values were not as impressive as those for the above CDR1 epitopes an d others usually present in low quantity, e.g. anti-V beta 2.1, 3.1 an d 24.1. Although there was great disparity between the MHC haplotypes of donors and recipients, and individual differences among patients, t he degree of restriction in the autoantibody response was surprising a nd suggests a common step in recognition and regulation of the respons e to allografts.