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The major histocompatibility complex (MHC, also called HLA or human leukocyte antigen) and its products have a central role in the immune response. Sharing of the MHC class II region is important for CD4+ (helper) T cell interactions, and sharing of the MHC class I region is important for CD8+ (cytotoxic) T cell interactions. This phenomenon is called MHC restriction of antigen-specific T cell responses.

The study of cerebrospinal fluid (CSF) cells in multiple sclerosis (MS) has been closely linked to progress in the field of general immunology. In the mid-70s, with the advent of the idea that MS was an immunologically-mediated disease (or, at least, that an immunological process was at the basis of its pathogenesis), there was a sudden fluorishing of research on CSF cells. In those years, immunological methods used to distinguish B from T lymphocytes were applied to CSF cells, in order to establish the relative percentage of T and B lymphocyte subsets. The challenge was to find some numerical or functional abnormality to explain the high production of IgG in MS CSF.