Enfermero

Antigen
tLudwig

presentation1
CEROTTINI1
School of Medicine,

EMIL R. UNANUE* AND JEAN-CHARLES *Department of Pathology, Washington University

St. Louis, Missouri 63110,

USA, and

Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland

ABSTRACT This paper reviews some of the cellular events involved in the immune recognition of foreign proteins. The recognitionof an antigen by T lymphocytes is essential for its effective elimination by the host. T lymphocytes of the CD4 or CD8 subset recognize antigen but only after the antigen is handled by antigen-handling cells (antigen-presenting cells). Antigen molecules are recognized after an internal processing event by antigenpresenting cells that results in the generation of immunogenic peptides. Such peptidesassociate with histocompatibility molecules to form bimolecular complexes on the cell surface. The T cell receptors for antigen recognize the bimolecular complex and initiate the events that result in an inflammatory response. Antigenpresenting cells also produce molecules - termed costimulators - that stimulate the growth and differentiation of T lymphocytes. -UNANUE, E. R., AND CEROTTINI, J.-C.Antigen presentation. FASEB j 3: 24962502; 1989. T

Key Words: antigen-presenting cells munogenic peptides T cell receptors

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lymphocytes
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CD4

CD8

PRESENTATION COMPRISES the cellular and biochemical events necessary for the recognition and stimulation of CD4 and CD8 T lymphocytes, the two essential T cell subsets responsible for the cellular events that result inthe elimination of foreign proteins, many bacteria, parasites, and viruses (reviewed in ref 1). Antigen presentation takes place between cells that take up the antigen, termed antigen-presenting cells (APCs), and the responding T cells, either of the CD4 and CD8 subsets. Knowledge of the nature of this interaction is critical for our understanding of basic T cell physiology. It is also critical inestablishing how ANTIGEN

symposium included the two authors of this retogether with Philip Stahl (Department of Cell Biology and Physiology, Washington University) and Ronald Schwartz (National Institutes of Health). For both the authors the symposium organized by the AAP was an important occasion. Twenty years ago we had worked together at the Scripps Clinic, trying to follow protein antigensin macrophages (2, 3). The macrophage is an APC found in most tissues. Originally described as a scavenger cell, it is now known to be critically involved in multiple interactions with T cells, including antigen presentation (1). Working under the limited technical conditions of that time, we were nonetheless impressed by the observation that antigen taken up by these cells was stronglyimmunogenic (4). Our results indicated that the immunogenic moiety had to be represented by very few molecules of antigen that remained cell associated after the bulk of the protein was rapidly catabolized. Since these early experiments, much has transpired, and at this point we have a considerably better perspective on the molecular and biochemical changes that proteins undergo to become immunogenic. Sinceour initial collaboration we have proceeded in different paths-one (E. R. U.) to study macrophages and CD4 helper T cells, the other (J. -C. C.) to study the interaction of virally infected or tumorbearing cells with CD8 cytolytic T cells. Both areas of study, however, have now become closely related insofar as their biochemistry and basic mechanisms are concerned. This paper is a brief review ofsome of the antigen presentation issues raised in the AAP symposium. view, THE BASIC INTERACTION

AAP

effective or ineffective an immune response will be. Indeed, from the perspective of our basic knowledge of
cell-to-cell interactions and communications, the APC T cell interactions represent a unique and ideal system to study. In the recent meeting in New Orleans various minisymposia...