Novel Diversity in Th1, Th2 Type Differentiation of Hemagglutinin-Specific T Cell Clones Elicited by Natural Influenza Virus Infection in Three Major Haplotypes (H-2b,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-Ad- or I-Ed-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-Ak-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.