Major Histocompatibility Complex Class I: Difference between revisions
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==Major Histocompatibility Complex (MHC) Class I: Historical Background== | ==Major Histocompatibility Complex (MHC) Class I: Historical Background== | ||
''Major Histocompatibility Complex'' (MHC) refers to a complex of closely linked genes first identified in the early to mid-20th century as being the major factors in the rejection of living tissue allografts (grafts between members of the same species). It was these studies that gave MHC its name. Many other genes contribute to tissue allograft rejection to minor degrees, and these were called ''minor histocompatibility genes''. MHC genes code for MHC proteins that are the major antigens responsible for tissue allograft rejection. George D. Snell received one third of the [http://nobelprize.org/nobel_prizes/medicine/laureates/1980/ 1980 Nobel Prize in Physiology or Medicine] for his contributions to the identification and characterization of these genes. Of course many other researchers made crucial contributions and they are credited in [http://nobelprize.org/nobel_prizes/medicine/laureates/1980/snell-lecture.pdf Snell's Nobel Lecture]. Jean Dausset received a third of the [http://nobelprize.org/nobel_prizes/medicine/laureates/1980/ 1980 Nobel Prize in Physiology or Medicine] for demonstrating the existence of MHC genes and proteins in humans, the latter being called ''Human Leukocyte Antigens'' ('''HLA'''). In mice, the most-used experimental model for studying MHC, the histocompatibility genetic loci were numbered H-1, H-2, H-3, and so forth. '''H-2''' is the major histocompatibility locus, while all the others are minor. Both HLA and H-2 turned out to be large complexes of closely-linked genes. | ''Major Histocompatibility Complex'' (MHC) refers to a complex of closely linked genes first identified in the early to mid-20th century as being the major factors in the rejection of living tissue allografts (grafts between members of the same species). It was these studies that gave MHC its name. Many other genes contribute to tissue allograft rejection to minor degrees, and these were called ''minor histocompatibility genes''. MHC genes code for MHC proteins that are the major antigens responsible for tissue allograft rejection. George D. Snell received one third of the [http://nobelprize.org/nobel_prizes/medicine/laureates/1980/ 1980 Nobel Prize in Physiology or Medicine] for his contributions to the identification and characterization of these genes. Of course many other researchers made crucial contributions and they are credited in [http://nobelprize.org/nobel_prizes/medicine/laureates/1980/snell-lecture.pdf Snell's Nobel Lecture]. Jean Dausset received a third of the [http://nobelprize.org/nobel_prizes/medicine/laureates/1980/ 1980 Nobel Prize in Physiology or Medicine] for demonstrating the existence of MHC genes and proteins in humans, the latter being called ''Human Leukocyte Antigens'' ('''HLA'''). In mice, the most-used experimental model for studying MHC, the histocompatibility genetic loci were numbered H-1, H-2, H-3, and so forth. '''H-2''' is the major histocompatibility locus, while all the others are minor. Both HLA and H-2 turned out to be large complexes of closely-linked genes. | ||
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==3D Structure and Its Significance== | ==3D Structure and Its Significance== | ||
By the mid-1980's, there was abundant evidence that the ability of T lymphocytes to recognize antigen is "restricted" by MHC. However, what this "restriction" meant in terms of molecular mechanism was far from clear. Speculation about possible mechanisms raged for over a decade following Zinkernagel and Doherty's 1975 insight. But no experimental evidence available at the time was able to explain the "restriction". As an illustration, Figure 7 in [http://nobelprize.org/nobel_prizes/medicine/laureates/1980/benacerraf-lecture.html Benacerraf's Nobel Lecture] shows his thinking in 1980. The figure shows an "Ia molecule" hypothetically "specifically interacting" with an "antigen fragment". Note that although the genetic linkage between Ia (the molecule coded for by immune response genes) and MHC was well established, it was not yet clear that Ia was MHC. Benacerraf's thinking was correct, as far as it went, but the details were not yet available. | By the mid-1980's, there was abundant evidence that the ability of T lymphocytes to recognize antigen is "restricted" by MHC. However, what this "restriction" meant in terms of molecular mechanism was far from clear. Speculation about possible mechanisms raged for over a decade following Zinkernagel and Doherty's 1975 insight. But no experimental evidence available at the time was able to explain the "restriction". As an illustration, Figure 7 in [http://nobelprize.org/nobel_prizes/medicine/laureates/1980/benacerraf-lecture.html Benacerraf's Nobel Lecture] shows his thinking in 1980. The figure shows an "Ia molecule" hypothetically "specifically interacting" with an "antigen fragment". Note that although the genetic linkage between Ia (the molecule coded for by immune response genes) and MHC was well established, it was not yet clear that Ia was MHC. Benacerraf's thinking was correct, as far as it went, but the details were not yet available. | ||
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==MHC Structure Tutorial== | ==MHC Structure Tutorial== | ||
A tutorial about the structure of MHC is available at [http://molviz.org MolviZ.Org]. It includes side by side comparisons of two different viral epitopes in MHC class I (with synchronized mouse rotation), of epitopes in MHC I vs. II, and a chapter on MHC class II structure. | A tutorial about the structure of MHC is available at [http://molviz.org MolviZ.Org]. It includes side by side comparisons of two different viral epitopes in MHC class I (with synchronized mouse rotation), of epitopes in MHC I vs. II, and a chapter on MHC class II structure. | ||
==Recognition of MHC by T Cell Receptor Mimetric Antibodies== | ==Recognition of MHC by T Cell Receptor Mimetric Antibodies== | ||
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==MHC Structures== | ==MHC Structures== | ||
A list of MHC structures is at [[Major histocompatibility complex]]. | A list of MHC structures is at [[Major histocompatibility complex]]. | ||
