6: Ch. Genetics of the MHC Locus and
Functions of the MHC Molecules
MBB/HSCI 426, MBB 726; Immune System I
Friday 14 October 2011
This lecture is taken from:
Ch 6: pp. 217-233
MHC Haplotype
HAPLOTYPE = the alleles on a given chromosome (i.e., LINKED alleles)
Mouse MHC nomenclature:
Kb (K molecule of the b haplotype)
I-Ad (I-A molecule of the d haplotype)
Studies using SYNGENEIC (= identical genotype) mice
ALLOGENEIC (= allelic genotype) mice are a different strain from a reference mouse. In
immunological studies, they are typically inbred mice that have a different MHC haplotype
from the reference strain under study.
XENOGENEIC = (= foreign genotype) different species.
CONGENIC means there is a single gene or region that is allelic between two mice.
Typically it refers to class I or II MHC genes. Mice of haplotype 1 are crossed on those
with haplotype 2, then repeatedly back-crossed on haplotype 1, but using mice that have
retained a specified haplotype-2 MHC molecule. After 20-30 generations of backcrossing,
the haplotype-2 MHC molecule should be on the haplotype-1 genetic background.
Figure cells 5-21
T Recognize Antigen
in the Context of MHC
RESTRICTION means that a MHC allele restricts recognition by a particular T
cell receptor.
This concept was first worked out by a combination of genetics and cellular
assays.
MHC Restriction Is Revealed by Adoptive Transfer Expts
Figure 7-28 transfer of BM cells,
Adoptive
including T-cell precursors & APCs,
into lethally irradiated recipient
mice (whose non-dividing stromal
cells live & dividing BM cells die.)
Immunize chimeric
mice with a
protein antigen
Incubate immune
T cells with APCs
loaded with antigen,
and measure T cell
proliferation by
following uptake of
tritiated [3H]
Appendix: T cell methods and materials
Antigen-specific T cells can
be cloned by (i) isolating
single cells (limiting
dilution), then (ii) growing
the cells on monolayers of
APCs loaded with antigen
and media containing the
growth factor IL-2.
Figure A-27
Antigen-specific T cells
can be propagated as
stable clones for many
generations.
Genes expressing T-cell
receptors from antigenspecific T cells can be
isolated from cDNA prepared
from the clones.
Figure A-32