MHC class Ia-restricted T cells partially account for beta 2-microglobulin-dependent resistance to Mycobacterium tuberculosis

Recent studies have highlighted the heterogeneous nature of the CD8(+) T ce ll response during human Mycobacterium tuberculosis infection; MHC class la , MHC class Ib and CD1 have all been identified as significant restriction elements. Here we have attempted to define the role of MHC class la in resi stance to M. tuberculosis infection in mice. The course of M. tuberculosis infection in mice deficient in a single MHC class la 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 la molecules (H2-K-b/H2-D-b double knockout mice) were substantially more susceptible to M. tuberculosi s infection. However, the double knockout mice were not as susceptible as b eta2-microglobulin-deficient mice, which have a broader phenotypic deficit. Thus, antigen presentation via MHC class la is an important component in r esistance to M. tuberculosis, but its absence only partially accounts for t he increased susceptibility of beta2-microglobulin-deficient mice.