H-2 alleles contribute to antigen 85-specific interferon-gamma responses during Mycobacterium tuberculosis infection

The in vitro immune responses to mycobacterial antigens have been linked to the H-2 loci in mice. We evaluated in vitro and in vivo immune responses during early Mycobacterium tuberculosis (M.tb) pulmonary infection of C57BL/6 (H-2b), C57BL/6 (H-2k), CBA/J (H-2k), and C3H/HeJ (H-2k) mice to determine H-2k-dependent and -independent effects. H-2k-dependent effects included delayed and diminished Ag85-specific Th1 cell priming, a reduced frequency of Ag85-specific IFN-γ producing cells, reduced IFN-γ protein in vivo, and increased M.tb lung burden as demonstrated by C57BL/6 H-2k mice vs. C57BL/6 mice. H-2k-independent factors controlled the amount of Ag85-specific IFN-γ produced by each cell, T cell numbers, granuloma size, and lymphocytic infiltrates in the lungs. Overall, these results suggest that an H-2k-dependent suboptimal generation of Ag85-specific cells impairs control of early M.tb growth in the lungs. H-2k-independent factors influence the potency of IFN-γ producing cells and immune cell trafficking during pulmonary M.tb infection.