Antigen Presentation to Lymphocytes

Abstract

Antigen presentation to T and B lymphocytes by antigen‐presenting cells plays a central role in the initiation and regulation of adaptive immune responses. T cells recognize peptides in the context of major histocompatibility complex (MHC) molecules. By contrast, B cells recognize proteins in a state of solution.

Keywords: T cell; B cell; dendritic cell(DC); MHC class I; MHC class II; antigen peptide

Figure 1.

Antigen presentation to T lymphocytes. (a) CD8+ cytotoxic T cells recognize antigenic peptides presented by class I major histocompatibility complex (MHC) molecules. (b) CD4+ helper T cells recognize antigenic peptides presented by class II MHC molecules. (c) Certain T‐cell populations, including natural killer (NK) T cells and γδ T cells, recognize lipid and glycolipid antigens presented by MHC‐related molecules, CD1.

Figure 2.

Processing of endogenous and exogenous proteins into peptides that are going to be loaded on to MHC molecules. Nearly 30% of newly synthesized proteins are for some reason misfolded. Even intact endogenous proteins are denatured by various sources of stress like heat shock. Those unfolded proteins are rapidly ubiquitinylated by ubiquitin‐specific activating enzyme (E1), conjugating enzyme (E2) and ubiquitin ligase (E3). The polyubiquitinylated proteins are degraded by the proteasome into peptides some of which are loaded on to MHC class I molecules in the ER. On the other hand, internalized exogenous proteins or even endogenous proteins engulfed by autophagosome are transported into the endosome/MIIC compartment and degraded by acid proteases. The produced peptides are loaded on to MHC class II molecules that have been escorted by the invariant chain (Ii) to MIIC compartment.

Figure 3.

Antigen presentation to B lymphocytes by follicular dendritic cells (FDCs) in a germinal centre. B cells undergo rapid proliferation accompanied by somatic hypermutation in their rearranged immunoglobulin genes, resulting in the generation of both antigen‐specific high‐affinity B cells and B cells that no longer recognize the antigen. High‐affinity B cells that recognize antigens presented by FDCs survive and differentiate, with the help of T cells, into either memory or plasma (antibody‐secreting) cells. In contrast, B cells that no longer recognize the antigen die through programmed cell death (apoptosis).

close

References

Brachet V, Raposo G, Amigorena S and Mellman I (1997) Ii chain controls the transport of major histocompatibility complex class II molecules to and from lysosomes. Journal of Cell Biology 137: 51–65.

Dengjel J, Schoor O, Fischer R et al. (2005) Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proceedings of the National Academy of Sciences of the USA 102: 7922–7927.

Goodnow CC (1996) Balancing immunity and tolerance: deleting and tuning lymphocyte repertoires. Proceedings of the National Academy of Sciences of the USA 93: 2264–2271.

Heath WR and Carbone FR (2001) Cross‐presentation, dendritic cells, tolerance and immunity. Annual Review of Immunology 19: 47–64.

Kosco MH (1991) Antigen presentation to B cells. Current Opinion in Immunology 3: 336–339.

Kyewski B and Klein L (2006) A central role for central tolerance. Annual Review of Immunology 24: 571–606.

Liu YJ, de Bouteiller O and Fugier‐Vivier I (1997) Mechanisms of selection and differentiation in germinal centers. Current Opinion in Immunology 9: 256–262.

McHeyzer‐Williams LJ and McHeyzer‐Williams MG (2005) Antigen‐specific memory B cell development. Annual Review of Immunology 23: 487–513.

Nakagawa TY and Rudensky AY (1999) The role of lysosomal proteinases in MHC class II‐mediated antigen processing and presentation. Immunological Reviews 172: 121–129.

Pamer E and Cresswell P (1998) Mechanisms of MHC class I‐restricted antigen processing. Annual Reviews in Immunology 16: 323–358.

Rammensee HG, Falk K and Rotzschke O (1993) Peptides naturally presented by MHC class I molecules. Annual Review in Immunology 11: 213–244.

Rock KL and Goldberg AL (1999) Degradation of cell proteins and the generation of MHC class I‐presented peptides. Annual Review in Immunology 17: 739–779.

Saric T, Chang SC and Hattori A (2002) An IFN‐gamma‐induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I‐presented peptides. Nature Immunology 3: 1169–1176.

Schubert U, Anton LC, Gibbs J et al. (2000) Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404: 770–774.

Serwold T, Gonzalez F, Kim J, Jacob R and Shastri N (2002) ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum. Nature 419: 480–483.

Sugita M, Moody DB, Jackman RM et al. (1998) CD1–a new paradigm for antigen presentation and T cell activation. Clinical Immunology and Immunopathology 87: 8–14.

Tanaka K, Tanahashi N, Tsurumi C, Yokota KY and Shimbara N (1997) Proteasomes and antigen processing. Advances in Immunology 64: 1–38.

Townsend A and Bodmer H (1989) Antigen recognition by class I‐restricted T lymphocytes. Annual Review of Immunology 7: 601–624.

Townsend SE and Goodnow CC (1998) Abortive proliferation of rare T cells induced by direct or indirect antigen presentation by rare B cells in vivo. The Journal of Experimental Medicine 187: 1611–1621.

van Kooten C and Banchereau J (1997) Functions of CD40 on B cells, dendritic cells and other cells. Current Opinion in Immunology 9: 330–337.

Further Reading

Carbone FR, Kurts C, Bennett SRM, Miller JFAP and Heath WR (1998) Cross‐presentation: a general mechanism for CTL immunity and tolerance . Immunology Today 19: 368–373.

Germain RN (1993) Antigen processing and presentation. Paul WE (ed.)s) Fundamental Immunology. New York: Raven Press.

Porcelli SA, Segelke BW, Sugita M, Wilson IA and Brenner MB (1998) The CD1 family of lipid antigen‐presenting molecules. Immunology Today 19: 362–368.

Robertson M (1998) Antigen presentation. Current Biology 8: 829–831.

Roitt IM, Brostoff J and Male DK (1989) Immunology. London: Gower Medical Publishing.

Whitton JL (1998) An overview of antigen presentation and its central role in the immune response. Current Topics in Microbiology and Immunology 232: 1–13.

Rock KL and Goldberg AL (1999) Degradation of cell proteins and the generation of MHC class presented peptides. Annual Review of Immunology 17: 739–779.

Kloetzel PM and Ossendrop F (2004) Proteasome and peptidase function in MHC‐class‐T‐mediated antigen presentation. Current Opinion in Immunology 16: 76–81.

Pamer E and Cresswell P (1998) Mechanisms of MHC class T‐restricted antigen processing. Annual Review of Immunology 16: 323–358.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Udono, Heiichiro, Wang, Jiyang O, and Watanabe, Takeshi(Apr 2007) Antigen Presentation to Lymphocytes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001227.pub2]