Casting a wider net: Immunosurveillance by nonclassical MHC molecules

• Type of Material: Article
• Authors: M. Patricia D'Souza, National Institute of Allergy and Infectious Diseases; Erin Adams, University of Chicago; John Altman, Emory University; Michael E. Birnbaum, Massachusetts Institute of Technology; Cesar Boggiano, National Institute of Allergy and Infectious Diseases; Giulia Casorati, San Raffaele Scientific Institute; Yueh-hsiu Chien, Stanford University; Anthony Conley, National Institute of Allergy and Infectious Diseases; Sidonia Barbara Guiomar Eckle, University of Melbourne; Klaus Fruh, Oregon Health and Science University; Timothy Gondre-Lewis, National Institute of Allergy and Infectious Diseases; Namir Hassan, Immunocore Ltd; Huang Huang, Stanford University; Lakshmi Jayashankar, National Institute of Allergy and Infectious Diseases; Anne G. Kasmar, Bill & Melinda Gates Foundation; Nina Kunwar, National Institute of Allergy and Infectious Diseases; Judith Lavelle, National Institute of Allergy and Infectious Diseases; David M. Lewinsohn, Oregon Health and Science University; Branch Moody, Brigham & Womens Hospital; Louis Picker, Oregon Health and Science University; Lakshmi Ramachandra, National Institute of Allergy and Infectious Diseases; Nilabh Shastri, University of California Berkeley; Peter Parham, Stanford University; Andrew J. McMichael, University of Oxford; Jonathan W. Yewdell, National Institute of Allergy and Infectious Diseases
• Language: English
• Date: 2019-02-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open access article, free of all copyright
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1007567
• Title of Journal or Parent Work: PLoS Pathogens
• ISSN: 1553-7366
• Volume: 15
• Issue: 2
• Start Page: e1007567
• End Page: e1007567
• Grant/Funding Information: The authors received no specific funding.
• Keywords: Virology; HLA-E; ANTIGEN; TUBERCULOSIS; COMPLEX; OPEN CONFORMERS; POPULATION; T-CELL RESPONSES; BINDING; HIGHLY PATHOGENIC SIV; Microbiology; Science & Technology; PEPTIDE REPERTOIRE; Life Sciences & Biomedicine; Parasitology
• Research Categories: Biology, Parasitology; Health Sciences, Public Health; Biology, Microbiology

Abstract

Most studies of T lymphocytes focus on recognition of classical major histocompatibility complex (MHC) class I or II molecules presenting oligopeptides, yet there are numerous variations and exceptions of biological significance based on recognition of a wide variety of nonclassical MHC molecules. These include αβ and γδ T cells that recognize different class Ib molecules (CD1, MR-1, HLA-E, G, F, et al.) that are nearly monomorphic within a given species. Collectively, these T cells can be considered “unconventional,” in part because they recognize lipids, metabolites, and modified peptides. Unlike classical MHC-specific cells, unconventional T cells generally exhibit limited T-cell antigen receptor (TCR) repertoires and often produce innate immune cell-like rapid effector responses. Exploiting this system in new generation vaccines for human immunodeficiency virus (HIV), tuberculosis (TB), other infectious agents, and cancer was the focus of a recent workshop, “Immune Surveillance by Non-classical MHC Molecules: Improving Diversity for Antigens,” sponsored by the National Institute of Allergy and Infectious Diseases. Here, we summarize salient points presented regarding the basic immunobiology of unconventional T cells, recent advances in methodologies to measure unconventional T-cell activity in diseases, and approaches to harness their considerable clinical potential.