PLASMODIUM FALCIPARUM-SPECIFIC T-CELL CLONES FROM NON-EXPOSED AND EXPOSED DONORS ARE HIGHLY DIVERSE IN TCR BETA-CHAIN V-SEGMENT USAGE

Humans lacking previous exposure to Plasmodium falciparum typically ha ve a high frequency of malaria-reactive T cells in peripheral blood, w hich cross-react with antigens from other microorganisms. We studied a large number of malaria-specific human T cell clones from nonexposed and malaria-exposed donors to determine whether this response is oligo clonal, and might therefore be generated by a limited number of cross- reactive epitopes, Most clones responded well to schizont antigen from three antigenically distinct stocks of P. falciparum. Clones derived from the same donor tended to show similar patterns of reactivity to a panel of non-malaria antigens from various microorganisms, suggesting that a limited number of epitopes were recognized by individuals, How ever, analysis of the usage of V segments of the beta chain of the TCR (TCRBV) revealed no evidence of TCRBV restriction in the T cell respo nse, either within individual donors or across ail donors. An apparent skewing towards TCRBV8 in one donor was shown by two methods to be du e to in vitro expansion of a single clone: (i) Direct sorting of TCRBV 8(+) CD4(+) T cells from fresh PBMC did not reveal any enrichment for pRBC-reactive cells; (ii) Sequencing of VDJ regions revealed that the TCRBV8 clones were identical, Sequences of non-TCRBV8 clones from this donor showed major differences in the VDJ junctional region. No diffe rences in TCRBV repertoire between non-exposed and exposed donors were observed, These results exclude the existence of a malarial superanti gen and suggest that the T cell response to malaria schizont antigen i n nonexposed donors is driven by a large number of epitopes.