MHC class II molecules are a family of molecules normally found only on
antigen-presenting cells such as dendritic cells, mononuclear phagocytes,
some endothelial cells, thymic epithelial cells, and B cells.
The antigens presented by class II peptides are derived from extracellular
proteins; hence, the MHC class II-dependent pathway of antigen
presentation is called the endocytic or exogenous pathway.
Loading of a MHC class II molecule occurs by phagocytosis; extracellular
proteins are endocytosed, digested in lysosomes, and the resulting epitopic
peptide fragments are loaded onto MHC class II molecules prior to their
migration to the cell surface. Structure
Like MHC class I molecules, class II molecules are also heterodimers, but in
this case consist of two homogenous peptides, an α and β chain, both of
which are encoded in the MHC. The subdesignation α1, α2, etc. refers to
separate domains within the HLA gene; each domain is usually encoded by a
different exon within the gene, and some genes have further domains that encode
leader sequences, transmembrane sequences, etc.
Because the antigen-binding groove of MHC class II molecules is open at both
ends while the corresponding groove on class I molecules is closed at each end,
the antigens presented by MHC class II molecules are longer, generally between
15 and 24 amino acid residues long. Expression
These molecules are constitutively expressed in professional, immune
antigen presenting cells, but may also be induced on other cells by interferon
γ. MHC class II is also expressed on group
3 innate lymphoid cells. Reaction to bacteria
Because class II MHC is loaded with extracellular proteins, it is mainly
concerned with presentation of extracellular pathogens. Class II
molecules interact mainly with immune cells, like the T helper cell . The
helper T cells then help to trigger an appropriate immune response which may
include localized inflammation and swelling due to recruitment of
phagocytes or may lead to a full-force antibody immune response due to
activation of B cells. Synthesis
During synthesis of class II MHC in the endoplasmic reticulum, the α and β
chains are produced and complexed with a special polypeptide known as the
invariant chain. The nascent MHC class II protein in the rough ER has its
peptide-binding cleft blocked by the invariant chain to prevent it from
binding cellular peptides or peptides from the endogenous pathway.
The invariant chain also facilitates the export of class II MHC from the ER to
the golgi, followed by fusion with a late endosome containing endocytosed,
degraded proteins. The invariant chain is then broken down in stages by
proteases called cathepsins, leaving only a small fragment known as CLIP
which maintains blockage of the peptide binding cleft on the MHC molecule. An
MHC class II-like structure, HLA-DM, facilitates CLIP removal and allows the
binding of peptides with higher affinities. The stable class II MHC is
then presented on the cell surface. Genes
Pathways controlling MHC class II antigen presentation
= Pathway: PSD4 - ARL14/ARF7 - MYO1E = Molecules involved
Several molecules are involved in this pathway.
- PIK3R2 and PIP5K1A are two kinases that create substrates for PSD4.
- PSD4 is a GEF that loads ARL14/ARF7 with GTP.
- ARL14/ARF7 is a Small GTPase protein that is selectively expressed in immune
cells. This protein is localized within MCH-II compartments in immature
Dendritic Cells. - ARF7EP is an effector of ARL14/ARF7
that interacts with MYO1E. - MYO1E is a protein that controls
MHC-II compartments with an actin-based mechanism.
Pathway PIK3R2 and PIP5K1A are two Kinases that
phosphorylates Phosphatidylinositol providing PSD4 with substrates for its
GTP loading ability. PSD4 as a Guanine Exchange Factor, loads ARL14/ARF7 with
GTP. Subsequently, ARF7EP interacts with MYO1E which binds itself to Actin
myofibers. Altogether, this complex contributes to maintain MHC-II loaded
vesicles within the Immature Dendritic Cell, impeding its translocation to Cell
Membrane. See also
Cross-presentation References
External links Histocompatibility Antigens Class II at
the US National Library of Medicine Medical Subject Headings
MHC Class II Genes at the US National Library of Medicine Medical Subject
Headings http:www.merck.comsec13ch163a.html