MHC class Ia-restricted T cells partially account for beta2-microglobulin-dependent resistance to Mycobacterium...

Recent studies have highlighted the heterogeneous nature of the CD8(+) T cell response during human Mycobacterium tuberculosis infection; MHC class Ia, MHC class Ib and CD1 have all been identified as significant restriction elements. Here we have attempted to define the role of MHC class Ia in resistance to M. tuberculosis infection in mice. The course of M. tuberculosis infection in mice deficient in a single MHC class Ia molecule, either H2-K(b) or H2-D(b), was essentially identical to that observed in wild-type mice. In contrast, mice fully deficient in MHC class Ia molecules (H2-K(b) / H2-D(b) double knockout mice) were substantially more susceptible to M. tuberculosis infection. However, the double knockout mice were not as susceptible as beta 2-microglobulin-deficient mice, which have a broader phenotypic deficit. Thus, antigen presentation via MHC class Ia is an important component in resistance to M. tuberculosis, but its absence only partially accounts for the increased susceptibility of beta 2-microglobulin-deficient mice.