Standard Article

Non-Classical MHC Class I Molecules (MHC-Ib)

  1. Rachel L Allen,
  2. L Hogan

Published Online: 15 NOV 2013

DOI: 10.1002/9780470015902.a0024246



How to Cite

Allen, R. L. and Hogan, L. 2013. Non-Classical MHC Class I Molecules (MHC-Ib). eLS. .

Author Information

  1. St George's, University of London, London, UK

Publication History

  1. Published Online: 15 NOV 2013


Major histocompatibility complex class I (MHC-I) molecules are a family of structurally related proteins that were first characterised through their central role in adaptive immunity. Classical MHC class I (MHC-Ia) molecules comprise a heavy chain complexed with β2m to display short peptide fragments on the surface of all nucleated cells. As antigen-presenting proteins, the classical role of MHC-Ia is to present these peptides for recognition by T-cell receptors expressed by cytotoxic T-cells. MHC-Ia are also recognised by innate immune receptors on other leukocyte subsets. A diverse group of structurally related proteins, collectively termed nonclassical MHC class I molecules or MHC-Ib, exists to perform a range of alternative immune roles. Here, the authors describe the biology of human MHC-Ib molecules and their recognition as antigen-presenting and antigen-independent ligands for various immune receptors.

Key Concepts:

  • Classical MHC class I (MHC-Ia) are highly polymorphic proteins which, together with β2m, form a structure that presents short peptide antigens for recognition by the classical αβ T-cell receptor (TCR) on CD8+ T-cells.

  • MHC-Ia proteins also exist in nonclassical forms – MHC-I heavy chain structures lacking β2m are found on the surface of activated immune cells, where they are recognised by alternative immune receptors such as members of the leukocyte Ig-like (LILR) family.

  • Nonclassical MHC-Ib are usually nonpolymorphic and tend to show a more restricted pattern of expression than their MHC-Ia counterparts.

  • MHC-Ib may be recognised by specific subsets of T-cell receptors or by innate immune receptors.

  • Owing to their recognition by a more restricted set of receptors, MHC-Ib are able to elicit a rapid response from immune cells and are, therefore, regarded as part of the innate immune system.

  • Some MHC-Ib act as antigen presenting structures, whereas others are recognised as direct ligands for immune receptors.


  • MHC-Ib;
  • HLA-E;
  • HLA-F;
  • HLA-G;
  • CD1;
  • MICA;
  • MICB;
  • ULBP;
  • NKT cells;
  • γδ T-cells