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CD1 and MR1 are major histocompatibility complex (MHC) class I-related proteins that bind and present non-peptide antigens to subsets of T cells with specialized functions. CD1 proteins typically present lipid antigens to CD1-restricted T cells, whereas MR1 presents vitamin B-based ligands and a variety of drugs and drug-like molecules to MR1-restricted T cells. The CD1 family of antigen presenting molecules has been divided into two groups: Group 1 contains CD1a, CD1b and CD1c, and Group 2 contains CD1d. Additionally, CD1e is expressed intracellularly and is involved in the loading of lipid antigens onto Group 1 CD1 proteins. Humans express both Groups 1 and 2 CD1 proteins, whereas mice only express CD1d. Group 1 CD1 proteins present lipid antigens to T cells that generally express diverse T cell receptors (TCRs) and exhibit adaptive-like functions, whereas CD1d presents lipid antigens to subsets of T cells that express either diverse or highly restricted TCRs and exhibit innate-like functions. CD1d-restricted T cells are called natural killer T (NKT) cells, which includes Type I or invariant NKT (iNKT) cells expressing semi-invariant TCRs, and Type II NKT cells expressing more diverse TCRs. CD1-restricted T cells have been implicated in a wide variety of diseases, including cancer, infections, and autoimmune, inflammatory and metabolic diseases. Additionally, NKT cells have been targeted for immunotherapy of disease with ligands such as α-galactosylceramide for iNKT cells, or sulfatide for Type II NKT cells. Like iNKT cells, MR1-restricted T cells express semi-invariant TCRs and display innate-like functions. MR1-restricted T cells, also called mucosal-associated invariant T (MAIT) cells, have been implicated in immune responses against a variety of pathogens such as Mycobacterium tuberculosis, Pseudomonas aeruginosa, Helicobacter pylori, hepatitis C virus and influenza virus. Moreover, these cells contribute to autoimmune and inflammatory diseases, including colitis, rheumatoid arthritis, psoriasis, lupus, and diabetes.

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.