Figure 3-25 Map of the Human Major Histocompatibility Complex 4 Mb (4,00,000 base pairs) on chromosome 6 with 200 genes Remember, class I MHCs are single proteins: Class II are dimers: Unlinked beta-2-microglobin

CYTOTROPHOBLAST EXPRESSION EXCHANGES CLIP FOR PEPTIDE Figure 3-23 Classical MHC genes CYTOTROPHOBLAST EXPRESSION EXCHANGES CLIP FOR PEPTIDE

1698 2271 1213 Beta-2 microglobin is monomorphic 32 149 44 158 7 1074

Other genes in the class II MHC Figure 3-27 Other genes in the class II MHC Tapasin (ER chaperonin) LMP2 and LMP7 proteasome subunits (induced by interferon) TAP1 and TAP2 peptide transporter pseudogenes

Co-dominant expression of MHCs

* * * * Mom and Dad class II heterodimers * Coexpression of MHCs by F1 mouse Mom and Dad class II heterodimers * MOUSE CELL * * * *

0.5% cross-over rate

Santos PS, Schinemann JA, Gabardo J, Bicalho Mda G. Horm. Behav Santos PS, Schinemann JA, Gabardo J, Bicalho Mda G. Horm. Behav. 2005 Apr;47(4):384-8. New evidence that the MHC influences odor perception in humans: a study with 58 Southern Brazilian students. Increasing evidence suggests a correlation between mate choice, odor preference, and genetic similarity at the Major Histocompatibility Complex (MHC) in a variety of animals, including our species. The MHC is a highly polymorphic group of genes that play an important role in the immunological self/nonself recognition. Its products have been reported to take part on the variety of compounds and reactions that together build an individual's body odor. It has been suggested, therefore, that animals use body odor as a guide to identify possible mates as MHC-similar or MHC-dissimilar from their own genotype. Preference for a MHC-dissimilar partner enhances MHC heterozygosity of an individual's offspring. The possible adaptive advantages are clear: it is a mechanism of avoiding inbreeding and MHC-heterozygous offspring may have enhanced immunocompetence. The aim of this study was to search, in our species, new evidence on the correlation between specificities at HLA-A and HLA-B and assessments of pleasantness regarding specific body odors. HLA is the name for the human MHC. Four olfactory sessions were performed with 58 young Southern Brazilian students, in order to investigate whether assessments of pleasantness of body odors from individuals correlate to a person's HLA phenotype. Body odors were collected via sweat and urine from all participants. Women smelled and scored all male odor samples and men did the same with all female samples. We found a significant correlation only when female smellers evaluated male sweat odors. http://www.youtube.com/watch?v=-drpViV5LSw

other strains may share MHC haplotype on different backgrounds. A and A.TL are recombinant haplotypes

Recipients reject foreign haplotype, accept (tolerate) haplotypes they share

How to make congenic (same MHC) mice

Peter Doherty and Rolf Zinkernagel  Nobel Prize 1996

CTLs are self-restricted (only respond to self MHCs)

Figure 3-30 The TCR must be able to recognize the MHC and the peptide. TCRs are restricted to recognizing self MHCs.

Let me think. You only reject non-self transplants, but you can only respond to self. Makes no sense! All T cells are self-restricted, BUT, a significant percentage (1-24%) of T cells are alloreactive (react to foreign MHCs). (Stay tuned)

Super antigens http://en.wikipedia.org/wiki/Rely_(brand) Toxic-shock syndrome toxin-1. Stapylococcal enterotoxin from Staphylococcus aureus. 1978