The document summarizes the major histocompatibility complex (MHC). It discusses how the MHC was discovered through studies of tissue transplantation in mice. The MHC locus contains genes that encode MHC class I and class II molecules that present antigens to T cells and play a key role in immune responses. MHC molecules are expressed on nearly all nucleated cells for class I and specifically on antigen presenting cells for class II. The genomic organization and structures of MHC class I and II molecules allow them to present peptides to CD8+ or CD4+ T cells, respectively.

1. z
Major Histocompatibility
Complex (MHC)
Dr Rohimah Mohamud
Department of Immunology
2017
REF: Celllular and Molecular Immunology by Abul Abbas Andrew Lichtman Shiv Pillai

2. z
Lecture objectives: MHC structure
and functions
 discovery of MHC and different definition used in
HLA system
 genomic organization and structure of class I and
class II MHC molecules
 expression of MHC molecules
 role of MHC in immune responses

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Discovery of the MHC: the mouse
MHC (H-2 complex)
 The MHC was discovered from studies of tissue
transplantation by George Snell and colleagues in 1940s
 They showed that a single genetic region is primarily
responsible for rapid rejection of tissue grafts - major
histocompatibility locus
 The particular locus linked to a gene on chromosome 17
encoding a blood group antigen called antigen II, and therefore
this region was named histocompatibility-2, or simply H-2.
 Initially, this locus was thought to contain a single gene that
controlled tissue compatibility.
 However, they found that occasional recombination events
occurred within the H-2 locus during interbreeding of different
strains, indicating that it contained several different but closely
linked genes
Page 117

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MHC molecules?
 The genetic region that controlled graft rejection and contained several
linked genes
 Human form of MHC is called Human leukocyte antigens (HLA)
 A large genetic locus (on human chromosome 6 and mouse chromosome 17) that
includes the highly polymorphic genes encoding the peptide-binding molecules
recognized by T lymphocytes. The MHC locus also includes genes encoding
cytokines, molecules involved in antigen processing, and complement proteins.

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Genomic organization of MHC
 Class I- encodes glycoproteins
expressed on the surface of nearly all
nucleated cell- the major function of the
class I gene is presentation of peptide
antigens to cytotoxic T cells (Cytotoxic
T Lymphocytes, CTL) = restricted to
CD8+ T cells
 Class II- encodes glycoproteins
expressed primarily on antigen-
presenting cells, eg: macrophages,
dendritic cells and B cells- present
processed peptides to T helper cells =
restricted to CD4+ T cells
 Class III- encodes various secreted
proteins that have immune function eg
C2,C4, Factor B, &TNF, and molecules
involved in inflammation.
Fig. 6.7, page 119

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Map of human MHC
Class I MHC genes:
HLA-A, HLA-B, and HLA-C
Class II HLA gene loci called:
HLA-DP, HLA-DQ, and HLA-
DR. Each class II MHC
molecule is composed of a
heterodimer
of α and β polypeptides, and
the DP, DQ, and DR loci each
contain separate genes
designated A or B,
encoding α and β chains,
respectively.

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General properties of MHC
molecules
• Each MHC molecule consists of an extracellular peptide-binding cleft, or groove, followed
by immunoglobulin (Ig)–like domains and transmembrane and cytoplasmic domains.
• The polymorphic amino acid residues of MHC molecules are located in and adjacent to
the peptide-binding cleft.
• The nonpolymorphic Ig-like domains of MHC molecules contain binding sites for the T cell
molecules CD4 and CD8.
Fig. 6.10, 6.12
page 124

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Expression of MHC molecules
• Class I molecules are constitutively
expressed on virtually all nucleated cells,
whereas class II molecules are expressed
only on dendritic cells, B lymphocytes,
macrophages
• WHY? This pattern of MHC expression is
linked to the functions of class I–restricted
and class II–restricted T cells.
▫ The effector function of class I–restricted
CD8+ CTLs is to kill cells infected with
intracellular microbes, such as viruses, as well
as tumors that express tumor antigens.
▫ In contrast, class II–restricted CD4+ helper T
lymphocytes have a set of functions that require
recognizing antigen presented by a more limited
number of cell types
Fig. 1.2, page 3

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Pathways of antigen processing
Fig. 6.14

10. z Pathways of antigen processing
Fig. 6.14

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Functions of APC
Fig. 6.2

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Lecture objectives: MHC structure
and functions
 discovery of MHC and different definition used in
HLA system
 genomic organization and structure of class I and
class II MHC molecules
 expression of MHC molecules
 role of MHC in immune responses

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Thank you
rohimahm@usm.my
Ext: 6248