Novel diversity in Th1, Th2 type differentiation of hemagglutinin- specific T cell clones elicited by natural influenza virus infection in three major 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 virus 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 three distinct antigenic peptides (p56-76, or p186-205 or p177-199), were uniformly Th1 type, releasing only IFN-γ on activation. In contrast, extensive diversity was evident for the C57BL/10 or CBA/Ca repertoire. Sibling T cell clones, established from the same C57BL/10 donor and expressing identical TCR β-chains in their recognition of p186-205, released either (IFN-γ and IL- 5) or (IFN-γ and IL-4 and IL-5) or (IL-4 and IL-5 and IL-10) following Ag- specific or nonspecific stimulation. Similarly, I-A(k)-restricted T cell clones, specific for p120-139 secreted either (IFN-γ only) or (IFN-γ and IL-5) or (IFN-γ and IL-2 and IL-5) on activation. Despite such phenotypic diversity within the individual's repertoire, all clones had been maintained under identical in vitro culture conditions. Moreover, sequence analyses of TCR β gene usage indicated that in most instances clones from the same donor expressed identical (VDJ)β rearrangements, indicative of a common progenitor cell. FACS analysis of cytoplasmic cytokine production confirmed that for the novel phenotype (IFN-γ and IL-5), both LKs were synthesized at the single cell level. Sibling families of T cell clones, established from a common donor following viral infection but differing in LK secretion, may offer a suitable model system for further studies of signal transduction mechanisms that discriminate between Th1- and Th2-specific responses to a well defined protective Ag.