Casting a wider net: Immunosurveillance by nonclassical MHC molecules

M. Patricia D’Souza, Erin Adams, John D. Altman, Michael E. Birnbaum, Cesar Boggiano, Giulia Casorati, Yueh Hsiu Chien, Anthony Conley, Sidonia Barbara Guiomar Eckle, Klaus Früh, Timothy Gondré-Lewis, Namir Hassan, Huang Huang, Lakshmi Jayashankar, Anne G. Kasmar, Nina Kunwar, Judith Lavelle, David M. Lewinsohn, Branch Moody, Louis PickerLakshmi Ramachandra, Nilabh Shastri, Peter Parham, Andrew J. McMichael, Jonathan W. Yewdell

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Article numbere1007567
JournalPLoS pathogens
Issue number2
StatePublished - Feb 2019

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology


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