Re: thanks! HLA vs. MHC but there is more...

From: Ulrich Beutner (beutner@chirurgie.uni-wuerzburg.de)
Date: Tue Sep 11 2001 - 03:31:12 EST


Sorry, I really regret to stretch this thread even longer and to even
correct such a highly accomplished contributor as Dr. Daskal,
however, I think, his effort to compress a six hour lecture
oversimplified some points:


>I am not sure that you got it fully straight. So here ia a 6 hour
>lecture block
>condensed into 60 seconds:
>HLA= Human Lymphocyte Antigens This is the equivalent to the mouse
>(mammalian)  MHC
>( Major Histocompatibility Complex).

MHC (all species if they have it), H-2 (mouse) and RT-1 (rat) refer
to a gene cluster containing the (major) genes responsible for tumor
and tissue rejection. As we know today many of the genes encode
proteins which present peptide antigens to T-cells. These proteins
are called HLA class I and class II in humans (or correspondingly in
other species, like SLA in swine). In one sentence: MHC refers to
genes, HLA to proteins.

>The MHC contain three groups of genes:
>class I, class II and clas III which control the following:
>Class I & class II code for surface recognition molecules
>class III codes for some complement components.

I think a better definition for class III is the genes not involved
in antigen presentation like TNF-a and some complement components.
However, this definition is not perfect either, because it would
exclude TAP-1 and LMP from class III, thus, a lot of people do not
like the term MHC class III. (N.B. for non immunologists: TNF, LMP,
TAP-1 are all encoded in the MHC, TNF-a is a cytokine, TAP-1 is
peptide transporter to translocate peptides from the cytoplasma to
the ER to be loaded on HLA class I molecules, LMP is involved in
generating these peptides)


>All nucleated cells express clas I MHC antigens on their surface
>class II on some Bcells, and macrophages, acivated cells (Tcells)
The list lacks the most prominent class II expressor: the dendritic
cells. Also I was under the impression that most if not all B-cells
express class II.
(N.B. there are even more cell types expressing class II and class II
expression is species dependent: activated mouse T-cells do not
express class II)

>In humans the HLA gene is located on chromosome #6. Class I genes code for
>transplantation antigens A, B and C
>Class II  genes are DP,DQ, DR and DZ.  Class III as we said are that
>of the complement
>system.
>The difference between the mouse and the human "MHC" is that in the
>human all the
>genes are linerly arranged and uninterupted while in the mouse the
>MHC the class I
>genes are interupted by Class  II and III.
>Hope thatb his made is simple but not simpler. Good luck!
>
>Ierachmiel Daskal M.D. PhD. FCAP, FASCP
>Chairman
>Department of Pathology and Laboratory Medicine
>(215) 456-6126
>Pager: 2-3559
>daskali@einstein.edu
>
>

For all people still confused, I can recommend to go to the library
and get Jan Klein's "Natural history of the MHC". Although clearly
outdated (1986) this book is highly readable, covers all the
questions discussed in this thread (in particular in the opening
chapter about the discovery of the MHC) and is probably the most
thorough work ever done about this topic (the list of references is
virtually endless and all references are sorted according to topics).

yours
Ulrich Beutner


--
================================================
Ulrich Beutner, Ph.D.
Chirurgische Universitaetsklinik
Abt.: Exp. Transplantationsimmunologie (ETI)
(University Hospital, Department of Surgery
Unit for Experimental Transplantation Immunology)
Josef-Schneider-Str. 2
97080 Wuerzburg
Germany

beutner@chirurgie.uni-wuerzburg.de

Tel.	++49 931 201-2252
FAX:	++49 931 201-3448 (or 2249)
=================================================



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