Nonclassical T Cells and Their Antigens in Tuberculosis

Abstract

Correspondence: gennaro_delibero@immunol.a-star.edu.sg T cells that recognize nonpeptidic antigens, and thereby are identified as nonclassical, represent important yet poorly characterized effectors of the immune response. They are present in large numbers in circulating blood and tissues and are as abundant as T cells recognizing peptide antigens. Nonclassical T cells exert multiple functions including immunoregulation, tumor control, and protection against infections. They recognize complexes of nonpeptidic antigens such as lipid and glycolipid molecules, vitamin B 2 precursors, and phosphorylated metabolites of the mevalonate pathway. Each of these antigens is presented by antigen-presenting molecules other than major histocompatibility complex (MHC), including CD1, MHC class I-related molecule 1 (MR1), and butyrophilin 3A1 (BTN3A1) molecules. Here, we discuss how nonclassical T cells participate in the recognition of mycobacterial antigens and in the mycobacterial-specific immune response.T he recognition by T lymphocytes of antigenic complexes formed by antigens and antigen-presenting molecules is a hallmark of the adaptive immune system. Awide range of exogenous and endogenous antigenic molecules reflecting a variety of chemical structures have been identified and are represented by proteins, lipids, phosphorylated metabolites, or vitamin B 2 pathway metabolites. The role of classical T cells, which recognize peptidic antigens associated with MHC-encoded molecules, during Mycobacterium tuberculosis (MTB) infection is well documented and studied for a long time (Cooper 2009). On the contrary, nonclassical T cells recognizing nonpeptidic antigens associated with non-MHC antigen-presenting molecules have been described more recently. They have also been identified as important contributors to host defense against infections, although many aspects of their physiological role still remain to be discovered. Based on the restriction molecule, antigen specificity, and T-cell receptor (TCR) structure, non-MHC-restricted T cells can be grouped into three categories: lipid-and glycolipid-specific CD1-restricted T cells, mucosal-associated invariant T (MAIT) MR1-restricted cells, and TCR gd BTN3A1-restricted T cells. In this article, we review critical issues of the basic immunobiology of non-MHC-restricted T cells related to recognition of Editors:

Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection

“…Nonclassically restricted T cells use invariant restriction molecules and can present peptidic and nonpeptidic antigens, including glycolipids (96) and TB-derived products (97,98). HLA-E-restricted CD8 ϩ T cells can recognize TB-derived peptides (98-100) and proliferate during active TB, compared to healthy controls (101).…”

OMIP‐058: 30‐Parameter Flow Cytometry Panel to Characterize iNKT, NK, Unconventional and Conventional T Cells

“…Vδ1 + and Vδ2 + Vγ9 + T cells are activated by distinct biochemical classes of antigens and differ in their phenotypic and functional characteristics (10). Vδ2 + Vγ9 + T cells expand during Mycobacterium tuberculosis infection and are capable of killing infected cells (21,22). In addition, viral infections such as CMV and HIV-1 drive Vδ1 + T cell expansion (10,19).…”

“…On the other hand, Vδ2 + T cells interact with phosphoantigens, which are synthesized by bacteria belonging to the genus of Mycobacteria, Listeria, and Salmonella as well as plasmodium species (1,20). Vδ2 + Vγ9 + T cells expand during Mycobacterium tuberculosis infection and are capable of killing infected cells (21,22). Interestingly, two populations within Vδ2 + Vγ9 + T cells exist with distinct expression levels of Vδ2 (Vδ2 low Vγ9 + and Vδ2 high Vγ9 + ) (Fig.…”

Mucosal-Associated Invariant T Cells Are Depleted and Exhibit Altered Chemokine Receptor Expression and Elevated Granulocyte Macrophage-Colony Stimulating Factor Production During End-Stage Renal Disease

“…More recently, non-conventional T cell populations such as invariant NKT (iNKT), γδ, and mucosal-associated invariant T (MAIT) cells have emerged as important bridges between the innate and adaptive immune systems ( 7 ). These cells contribute to host immunity against TB infection and a variety of other bacterial and viral pathogens ( 8 , 9 ), but their function in ESRD patients is poorly described.…”