NetNews Usenet Archive 1992 #31/NN_1992_31.iso/spool/sci/med/aids/2184

Text File | 1993-01-02 | 5.4 KB | 103 lines

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From: Billi Goldberg <[e-mail]>
Subject: Antigen Presenting Cells
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Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
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                     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.