Page 548 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 62 Major Histocompatibility Complex & Transplantation
TABLE 62–1 Comparison of Class I and Class II MHC Proteins
Feature
Class I MHC Proteins
Yes
Present antigen to CD4-positive cells
No
Yes
No
Present antigen to CD8-positive cells
Yes
No
Found on surface of all nucleated cells
1
Found on surface of “professional” antigen–presenting cells, such as dendritic
Yes
Yes
cells, macrophages, and B cells
Encoded by genes in the HLA locus
Yes
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Yes
Expression of genes is codominant
Yes
Yes
Yes
Multiple alleles at each gene locus
No
Composed of two peptides encoded in the HLA locus
Yes
Yes
Composed of one peptide encoded in the HLA locus and a β 2 -microglobulin
No
1
Note that class I MHC proteins are found on the surface of all nucleated cells, including those that have class II MHC proteins on their surface. Mature red blood cells are
nonnucleated; therefore, they do not synthesize class I MHC-proteins.
In addition to the major antigens encoded by the HLA
genes, there is an unknown number of minor antigens
These are glycoproteins found on the surface of antigen-
encoded by genes at sites other than the HLA locus. These
presenting cells, such as macrophages, B cells, dendritic
minor antigens can induce a weak immune response that can Class II MHC Proteins
cells of the spleen, and Langerhans’ cells of the skin. They
result in slow rejection of a graft. The cumulative effect of
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are highly polymorphic glycoproteins composed of two
several minor antigens can lead to a more rapid rejection
polypeptides that are noncovalently bound. Like class I
response. These minor antigens are various normal body
proteins, they have hypervariable regions that provide
proteins that have one or more amino acid differences from
one person to another (i.e., they are “allelic variants”).
which have only one chain encoded by the MHC locus
Because these proteins have an amino acid difference, they
(β -microglobulin is encoded on chromosome 15), both
2
are immunogenic when introduced as part of the donor graft
chains of the class II proteins are encoded by the MHC
tissue. There are no laboratory tests for minor antigens.
locus. The two peptides also have a constant region where
Between the class I and class II gene loci is a third locus
the CD4 proteins of the helper T cells bind.
(See Figure 62–1), sometimes called class III. This locus
contains several immunologically important genes, encod-
BIOLOGIC IMPORTANCE OF MHC
ing two cytokines (tumor necrosis factor and lymphotoxin)
and two complement components (C2 and C4), but it does
not have any genes that encode histocompatibility
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association of the antigen with either class I or class II pro-
antigens.
teins. For example, cytotoxic T cells respond to antigen in
association with class I MHC proteins. Thus a cytotoxic T
MHC PROTEINS
cell that kills a virus-infected cell will not kill a cell infected
with the same virus if the cell does not also express the
Class I MHC Proteins
appropriate class I proteins. This finding was determined by
mixing cytotoxic T cells bearing certain class I MHC pro-
These are glycoproteins found on the surface of virtually
teins with virus-infected cells bearing different class I MHC
all nucleated cells. There are approximately 20 different
proteins and observing that no killing of the virus-infected
proteins encoded by the allelic genes at the A locus, 40 at
the B locus, and 8 at the C locus. The complete class I pro-
Helper cell activity depends in general on both the recogni-
tein is composed of a 45,000-molecular-weight heavy chain
tion of the antigen on antigen-presenting cells and the pres-
noncovalently bound to a β -microglobulin. The heavy
ence on these cells of “self” class II MHC proteins. This
chain is highly polymorphic and is similar to an immuno- cells occurred. Helper T cells recognize class II proteins.
requirement to recognize antigen in association with a “self”
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globulin molecule; it has hypervariable regions in its
MHC protein is called MHC restriction. Note that T cells
N-terminal region. The polymorphism of these molecules
recognize antigens only when the antigens are presented on
is important in the recognition of self and nonself. Stated
another way, if these molecules were more similar, our abil-
MHC proteins), whereas B cells do not have that require-
ity to accept foreign grafts would be correspondingly
ment and can recognize soluble antigens in plasma with their
improved. The heavy chain also has a constant region
surface monomer IgM acting as the antigen receptor.
where the CD8 protein of the cytotoxic T cell binds.
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