Autoantibodies to T-cell receptor beta chains in human heart transplantation: epitope and spectrotype analyses and kinetics of response

Abstract

Autoantibodies against T-cell receptors have been found in two alloimmunization situations in humans: renal transplantation and pregnancy. We carried out longitudinal studies of human heart transplant recipients monitoring their autoantibody production to a recombinant single chain T-cell receptor V alpha/V beta construct, a set of nested, overlapping peptides duplicating the complete covalent structure of an individual T-cell receptor beta chain and a set of peptides duplicating the first 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 generated 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. However, some patients showed elevated responses as long as 12 months following the transplant. Autoantibody anti-CDR1 spectrotype analyses detected individual differences among patients, but 5 of 8 patients characterized in detail showed elevated IgG binding to CDR1 peptide epitopes 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 high, although the relative increases with respect to the pretransplant values were not as impressive as those for the above CDR1 epitopes and others usually present in low quantity, e.g. anti-V beta 2.1, 3.1 and 24.1. Although there was great disparity between the MHC haplotypes of donors and recipients, and individual differences among patients, the degree of restriction in the autoantibody response was surprising and suggests a common step in recognition and regulation of the response to allografts.