From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: Antigen Presenting Cells
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6704
Organization: unspecified
Date: Sat, 2 Jan 93 06:57:12 PST

                     ANTIGEN PRESENTING CELLS

There has been questions asked about the differing functions of Class I 
and Class II MHC on antigen presenting cells. Infected cells present on 
Class I MHC to T8 lymphocytes (CTL) while exogenous antigens are 
presented on Class II MHC to T4 lymphocytes (Helpers). There are CTLs of 
T4 lymphocytes, but this is only a very small percentage.

The following excerpt explains this functioning of antigen presenting 
cells better than anything else that I have read. I hope it will help 
explain this process to others.

I very, very strongly recommend the reading of Chapter 1 and Chapter 2 
of the book: "Biologic Therapy of Cancer." Chapter 1 has the most 
complete info on cytotoxic effector mechanisms that I have found 
anywhere. It is exciting to read how brilliantly Wunderlich and Hodes 
have tied together various sources to present a very cogent summary.
I believe the answer to AIDS is in the ability of cytotoxic effector 
mechanisms initiated by cellular immunity to control intracellular 
pathogens.

Chapter 2 is titled "Principle of Tumor Immunity: Biology of Antibody-
Mediated Responses."
------------------------------------------------------------------------

Chapter 1 Principles of Tumor Immunity: Biology of Cellular Immune 
Responses by John R. Wunderlich and Richard J. Hodes. The book is 
Biologic Therapy of Cancer (1991) edited by Vincent T. DeVita, Jr., 
Samuel Hellman and Steven A. Rosenberg; published by J.B. Lippincott 
Company.

John R. Wunderlich, MD is a Senior Investigator, Experimental Immunology 
Branch, DCBDC, National Cancer Institute, Bathesda, Maryland.

Richard J. Hodes, MD is also a Senior Investigator at NCI.

Page 10:

ANTIGEN PROCESSING AND PRESENTATION

In order to fulfill the first-signal requirements for T-cell activation, 
an APC must encounter antigen, process it, and present appropriate 
components (generally peptides) of antigen in association with Class I 
or Class II MHC determinants expressed on the APC surface. In the case 
of Class II-restricted antigen presentation, this requires that APCs 
themselves express Class II MHC products. For activation of some T 
cells, such as T-cell hybridomas, a signal consisting of MHC Class II 
molecules and foreign antigenic peptide is fully sufficient to trigger a 
response such as lymphokines (eg, IL-2) production. This activation can 
even be accomplished with synthetic lipid bilayers in which purified 
Class II (Ia) molecules have been inserted and which have been pulsed 
with antigenic peptide. However, when certain nontransformed antigen- 
specific T-cell lines are exposed to the same lipid bilayer, signaling 
of these T cells results in a limited response consisting of size change 
and IL-3 production, but no proliferation or IL-2 secretion. In fact, 
these T cells are rendered unresponsive so that they will not 
proliferate or secrete IL-2 in response to a subsequent challenge with 
normally stimulatory antigen-pulsed APCs. Thus, the "first signal" in 
the absence of other (second) signals can be tolerogenic [bg, clonal 
anergy]. This phenomenon, largely demonstrated in vitro, may have 
important in vivo correlates during the challenge of an intact organism 
with antigen.

Foreign antigens are generally encountered in the form of relatively 
large intact proteins, either in soluble form or on the surface of 
microorganisms or foreign cells. In order for most foreign antigens to 
be recognized by T cells, it appears that they must be processed into 
small soluble peptides, which are then presented in association with 
self MHC molecules. Antigens that are presented in association with self 
Class II MHC products appear to be primarily exogenous antigens that are 
taken up by APCs into endocytic vesicles. Within these vesicles, partial 
proteolysis occurs, generating peptides that then associate with Class 
II molecules either intracellularly or upon release at the cell surface. 
In contract, foreign antigens associated with self Class I MHC appear to 
be principally endogenously synthesized antigens, such as virally 
encoded products of infected cells. These antigens may associate with 
newly synthesized Class I molecules intracellularly or may be 
transported to the cell surface, where association subsequently takes 
place. The requirements for a competent APC thus include the ability to 
generate the signal provided by foreign antigen plus self MHC. Certain 
cell types appear to be broadly competent to provide this signal, as 
evidenced by their ability to stimulate resting T cells, as well as 
long-term T-cell lines and transformed T-cell lymphomas or hybridomas. 
Such cell types include dendritic cells, B lymphocytes, and cells of the 
monocyte-macrophage lineage. Other cell types, while not necessarily 
equivalent in their overall stimulatory ability, are able to stimulate 
certain T cells, such as T-cell hybridomas, and thus appear able to 
generate an antigen-specific first signal.
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