822
chapter
35
Molecular Immunology
cell r e c e p to r
c h a in
CO
r e c e p to r
c h a in
HTLV
P e p tid e
H LA -A .
[32 m ic ro g lo b u lin
c h a in
F I G I I R F 3 5 - 1 4
(Also see color figure.) Complex of MHC class I proteins, HTLV-1 peptide
(antigen) and TcR. The MHC class I proteins bind and present peptides
that are synthesized inside the infected cell to T-cell receptors (TcRs)
specific for the bound peptides. Interaction and stimulation of T-cell
proliferation occurs with CD8 positive, cytotoxic Tc cells. The figure is
derived from the coordinates published in the Protein Data Bank file 1BD2.
the MHC II protein thereby presenting the antigen to the
T cell (Figure 35-1).
Presentation of foreign (nonself)
peptides
by
the
MHC II protein to Th cells occurs in a similar manner
to the MHC I proteins, requiring both the MHC II pro-
tein and T-cell surface proteins of the CD3 complex (see
Table 35-1). The cell surface protein CD3 is involved in
transmembrane signaling and initiation of cytokine (im-
mune system messenger molecules) synthesis. Newly syn-
thesized and recycled MHC II proteins are, like the MHC I
proteins, “ushered” to the surface of the APC.
The MHC II antigen complex on the cell surface of also
contains two polypeptide chains,
a
and /3. The extracel-
lular polypeptide of the two chains each consists of two
domains, a 1 and
a l
and /11 and /12. Similar to the MHC I
complex, the peptide lies in a groove between the
a \
and
a2
domains. The structure of a human MHC II protein
and the CLIP peptide is shown in Figure 35-15. As noted
earlier, Recognition of the MHC II-peptide complex by
F I G U R F 3 5 -1 5
(Also see color figure.) Major histocompatibility complex (MHC) proteins
class II. The MHC class II proteins bind and present peptides that are
synthesized outside the infected cell, i.e., peptides that are derived from
proteins of the infecting organisms, bound to their specific T-cell receptors
(TcRs). Interaction and stimulation of T-cell proliferation occurs with
CD4+ T cells (Figure 35-16). The figure is derived from the coordinates
published in the Protein Data Bank file 1A6A.
the TcR on the T-helper cell occurs with the participation
of two other Th protein receptors: CD3 and CD4.
CD4 contains three domain structures: an extracellular
domain, a transmembrane domain, and an intracellular do-
main. The extracellular domain, which itself contains two
distinct immunoglobulin-like structures, interacts with the
TcR on the T-helper cell and with the MHC II protein
of the antigen-presenting cell. The transmembrane do-
main and the intracellular domain (not shown in the fig-
ure) are responsible for signaling to the inside of the
cell to which binding has occurred. The structure of two
immunoglobulin-like folds from a recombinant CD4 is
shown in Figure 35-16.
The glycoprotein, gp 120, part of the surface of the AIDS
virus (HIV-1), is responsible for the binding of virus to
the host cell. Although not an example of the region of
the antigen molecule that typically interacts, the struc-
ture of gpl20, an antibody Fab fragment, and CD4 is
shown in Figure 35-17. Gpl20 binds both to the CD4
