MHC class la-restricted T cells partially account for β2-microglobulin-dependent resistance to Mycobacterium tuberculosis

Abstract

Recent studies have highlighted the heterogeneous nature of the CD8+ T cell response during human Mycobacterium tuberculosis infection; MHC class Ia, MHC class lb and CD1 have all been identified as significant restriction elements. Here we have attempted to define the role of MHC class la in resistance to M. tuberculosis infection in mice. The course of M. tuberculosis infection in mice deficient in a single MHC class la molecule, either H2-Kb or H2-Db, was essentially identical to that observed in wild-type mice. In contrast, mice fully deficient in MHC class la molecules (H2-Kb/H2-Db double knockout mice) were substantially more susceptible to M. tuberculosis infection. However, the double knockout mice were not as susceptible as β2-microglobulin-deficient mice, which have a broader phenotypic deficit. Thus, antigen presentation via MHC class la is an important component in resistance to M. tuberculosis, but its absence only partially accounts for the increased susceptibility of β2-microglobulin-deficient mice.