Influence of antigenic experience on BJ gene segment usage in human CD4⁺ T cells

HLA molecules influence the selection of naive CD4⁺ T cells as demonstrated by HLA-DR-dependent differences in BV8-BJ frequencies. The repertoire of mature peripheral T cells utilized in antigen responses is shaped by additional factors such as antigens encountered in the environment. To identify mechanisms underlying the formation of the memory repertoire, differences in the BV8-BJ repertoire of CD45RO^- and CD45RO⁺CD4⁺ T cells were examined in 21 normal donors. The naive and memory CD4⁺ compartments displayed unique BV8-BJ repertoires in all individuals, demonstrating that the recruitment of CD4⁺ T cells into the memory population is a non-random process. The frequencies of selected BV8-BJ combinations were increased among CD45RO⁺ T cells. Size fractionation of such expanded BV8-BJ populations demonstrated that most of them were polyclonal in nature. Twenty-five percent of the expanded BV-BJ combinations included a dominant TCR sequence, indicating monoclonal proliferation. Selection of BV8-BJ combinations for preferential use among memory T cells was HLA dependent. HLA-DR1/4⁺ individuals were characterized by an increased usage of BV8-BJ2S7⁺ TCR, and decreased usage of BV8-BJ2S1⁺ and BV8-BJ2S2⁺ TCR, whereas HLA-DR3/7⁺ individuals preferentially recruited BV8-BJ2S5⁺ T cells, and disfavored BV8-BJ2S3⁺ and BV8-BJ2S7⁺ T cells. HLA-imposed effects on the naive and memory repertoire were distinct. The BV-BJ frequencies of CD45RO⁺ T cells could not be predicted from the pattern of TCR found in naive CD4⁺ T cells, suggesting that the HLA-DR polymorphisms influence thymic selection processes differently than peripheral selection forces.