Lcmv

infected

CTL recognizes viral peptide + self MHC

Strain A uninfected

Failure to recognize self peptide + self MHC

FIGURE 6-6 Experimental demonstration of the phenomenon of MHC restriction of T lymphocytes. Virus-specific cytotoxic T lymphocytes (CTLs) generated from virus-infected strain A mice kill only syngeneic (strain A) target cells infected with that virus. The CTLs do not kill uninfected strain A targets (which express self peptides but not viral peptides) or infected strain B targets (which express different MHC alleles than does strain A). By use of congenic mouse strains that differ only at class I MHC loci, it has been proved that recognition of antigen by CD8+ CTLs is self class I MHC restricted.

Failure to recognize viral peptide + allogeneic MHC

FIGURE 6-6 Experimental demonstration of the phenomenon of MHC restriction of T lymphocytes. Virus-specific cytotoxic T lymphocytes (CTLs) generated from virus-infected strain A mice kill only syngeneic (strain A) target cells infected with that virus. The CTLs do not kill uninfected strain A targets (which express self peptides but not viral peptides) or infected strain B targets (which express different MHC alleles than does strain A). By use of congenic mouse strains that differ only at class I MHC loci, it has been proved that recognition of antigen by CD8+ CTLs is self class I MHC restricted.

individual expresses the alleles that are inherited from each of the two parents. For the individual, this maximizes the number of MHC molecules available to bind peptides for presentation to T cells.

Class I and class II MHC genes are the most polymorphic genes present in the genome. The studies of the mouse MHC were accomplished with a limited number of strains. Although it was appreciated that mouse MHC genes were polymorphic, only about 20 alleles of each MHC gene were identified in the available inbred strains of mice. The human serologic studies were conducted on outbred human populations. A remarkable feature to emerge from the studies of the human MHC genes is the unprecedented and unanticipated extent of their polymorphism. The total number of HLA alleles in the population is estimated to be about 3500, with more than 250 alleles for the HLA-B locus alone. Molecular sequencing has shown that a single serologically defined HLA allele may actually consist of multiple variants that differ slightly. Therefore, the polymorphism is even greater than that predicted from serologic studies. As we shall discuss later in the chapter, the polymorphic residues of

FIGURE 6-7 Schematic maps of human and mouse MHC loci. The basic organization of the genes in the MHC locus is similar in humans and mice. Sizes of genes and intervening DNA segments are not shown to scale. Class II loci are shown as single blocks, but each locus consists of several genes. Class III MHC locus refers to genes that encode molecules other than peptide-display molecules; this term is not used commonly.

Human: HLA

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