NOVEL DIVERSITY IN TH1, TH2 TYPE DIFFERENTIATION OF HEMAGGLUTININ-SPECIFIC T-CELL CLONES ELICITED BY NATURAL INFLUENZA-VIRUS INFECTION IN 3MAJOR HAPLOTYPES (H-2(B,D,K))

We report novel diversity in the lymphokine (LK) secretion profile of hemagglutinin-specific, CD4(+) T cell clones elicited by influenza vir us infection in three major haplotypes: I-A(d)- or I-E-d-restricted T cell clones obtained from individual BALB/c donors, and specific for t hree distinct antigenic peptides (p56-76, or p186-205 or p177-199), we re uniformly Th1 type, releasing only IFN-gamma on activation. In cont rast, extensive diversity was evident for the C57BL/10 or CBA/Ca reper toire. Sibling T cell clones, established from the same C57BL/10 donor and expressing identical TCR beta-chains in their recognition of p186 -205, released either (IFN-gamma and IL-5) or (IFN-gamma and IL-4 and IL-5) or (IL-4 and IL-5 and IL-10) following Ag-specific or nonspecifi c stimulation. Similarly, I-A(k)-restricted T cell clones, specific fo r p120-139 secreted either (IFN-gamma only) or (IFN-gamma and IL-5) or (IFN-gamma and IL-2 and IL-5) on activation. Despite such phenotypic diversity within the individual's repertoire, all clones had been main tained under identical in vitro culture conditions. Moreover, sequence analyses of TCR beta gene usage indicated that in most instances clon es from the same donor expressed identical (VDJ)beta rearrangements, i ndicative of a common progenitor cell. FAGS analysis of cytoplasmic cy tokine production confirmed that for the novel phenotype (IFN-gamma an d IL-5), both LKs were synthesized at the single cell level, Sibling f amilies of T cell clones, established from a common donor following vi ral infection but differing in LK secretion, may offer a suitable mode l system for further studies of signal transduction mechanisms that di scriminate between Th1- and Th2-specific responses to a well defined p rotective Ag.