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

From: Larry Arnold (lwarma@med.unc.edu)
Date: Thu Sep 06 2001 - 14:48:36 EST 




Maciej



I haven't followed this whole thread so maybe I missed something but I
don't get the confusion that you derive from this paragraph. 
Everything is accurate.  As far as I see it there is no argument to
start.



Humans do have MHC Class I and II.  MHC stands for major
histocompatibility complex - i.e. all the genes and their
products that define the major histocompatibility system (i.e. those gene
products that lead to tissue rejection in the classical rapid way). 
All mammals (as well as other animals) have an MHC.  MHC is thus the
generic collective term for these genes/proteins and HLA is the term used
for the MHC system in humans.  HLA stands for human
lymphocyte antigen.  In the old days this
definition/term derived from the fact that the different gene products
that led to the rejection were defined on lymphocytes and detected using
the mixed lymphocyte reaction.  Even though the antigens were
defined on lymphocytes we now know that class I is expressed on nearly
all nucleated cells (and some others as was mentioned) while class II has
a much more limited distribution primarily on antigen presenting cells
including monocyte/macrophage, dendritic and B cells.  The reason
for the evolution of the 2 types derives from the need for afferent
antigen recognition and cell activation (known as antigen processing and
presentation) and efferent cell killing by cytotoxic T cells.  The
same system could not be used for both functions or it would have led to
the killing of any cell that had viral antigens (or other pathogen) -
whether the cell was actually infected or had simply taken up viral
proteins.  This would have lead to massive tissue destruction by the
CTLs.  The MHC contains quite a few genes.  In humans the major
groups are HLA-A, HLA-B, and HLA-C - the Class I MHC genes/proteins and
HLA-D the Class II MHC genes/products.  Also within the human
population each major group has many "polymorphisms" - i.e.
distinct types but still members of the group.  This polymorphism is
what leads to tissue rejection since we are outbred any given individual
is most likely to have different genes/proteins that will be recognized
as "foreign" by another individual.  Each human has the
potential for 2 different HLA-A, HLA-B, and HLA-C genes - one set from
each of your parents.  Each class I gene product is a single
glycoprotein non-covalently associated with beta2-microglobulin (and a
peptide of course but we'll leave that aside for now).  HLA-D (human
MHC class II) is more complicated because there are more genes (DR, DP,
DQ etc) and because class II proteins are composed of 2 different
proteins - alpha and beta to form a heterodimer (there is also the bound
peptide of course). Some loci have multiple alpha and/or beta genes which
may combine in different combinations leading to different heterodimer
molecules.  All of the MHC molecules are codominant - i.e all the
genes are expressed- so each cell will express 6 MHC class I ( 2 each of
HLA-A,B,C) molecules and, on the appropriate cell types many class II
(HLA-D) molecules.



I hope this helps with your confusion and doesn't start any
arguments.  Any basic immunology text will tell all of the
above.



Larry





At 06:56 PM 9/5/2001, you wrote:


I asked a few friends of mine who
are in various (reputable) medical

schools about MHC vs. HLA.  When they took the 6 week course 
in

immunology as 2nd year students, they were told humans have MHC
class

I and II. An immuno/microbio board review book I picked up at a

library also discusses MHC class I and II, in humans. So the

confusion is wide spread


I don't want to start an argument, but I just thought I'd mention
it.







Larry W. Arnold, Ph.D.

Res. Assoc. Prof.

Director, Flow Cytometry Facility

Department of Microbiology and Immunology

Lineberger Comprehensive Cancer Center

CB# 7290

University of North Carolina at Chapel Hill

Chapel Hill, NC 27599

Phone: 919-966-1530

FAX: 919-962-8103












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