REPERTOIRE BREADTH OF HUMAN CD4(-CELLS SPECIFIC FOR HIV GP120 AND P66(PRIMARY ANTIGENS) OR FOR PPD AND TETANUS TOXOID (SECONDARY ANTIGENS)() T)

Antigen derived peptides bound on MHC class II molecules on presenting cells stimulate specific CD4 lymphocytes that are in a naive state if antigen is given for the first time, or in a memory state if antigen has been previously encountered. In order to compare clonal heterogene ity of the human CD4(+) T helper repertoire in primary vs. recall resp onses, we have generated T cell lines in vitro by repeated stimulation of peripheral lymphocytes with primary or with recall antigens. Clona l heterogeneity was bred in the case of recall response to tetanus tor oid or PPD, with a high frequency of specific precursors (>100 cells/1 0(6) lymphocytes). In contrast, T cell lines responsive to primary ant igens (HIV gp120 or HIV p66) were oligoclonal as defined by TCR V beta gene usage and by spectratyping, and the precursor frequency was low (<2 cells/10(6) lymphocytes). Primary T cell lines generated from bloo d samples drawn at different times from the same donor showed that clo nes with identical TCR CDR3 region coding sequences were expanded, sug gesting that in these individuals a large progeny derived from one sin gle precursor is present, even though a previous encounter with I-he a ntigen was not documented. Assuming an even in viva distribution of su ch cells, the presence of one precursor every 10(6) CD4 lymphocytes (w ithin the CD4 T repertoire that comprises roughly 10(11) CD4 T cells) indicates that approximately 10(5) identical T cells from the same clo nal precursor account for the primary response against the model antig ens we have studied. (C) American Society for Histocompatibility and I mmunogenetics, 1998. Published by Elsevier Science Inc.