Extensive allelic polymorphism in the CDR2-like region of the miniature swine CD4 molecule.
MHC class II polymorphism is well documented whereas only minimal polymorphism has been reported for the CD4 molecule with which it interacts. We report on the structural basis of an allelic polymorphism of the CD4 molecule in miniature swine. Eleven of 13 nucleotide differences between the 2 alleles cause amino acid replacements. A majority of these replacements are clustered in a region protruding as a loop structure, termed Ig CDR2-like, from the surface of the amino terminal domain. This part of the human CD4 appears to comprise the binding site for the human immunodeficiency virus gp120 protein. The loop structure has also been implicated in the binding of CD4 to MHC class II, but this is currently a matter of some controversy. Our previous results have indicated that the porcine CD4 polymorphism, that we now show is situated in this loop, does not significantly affect the binding to class II. However, because the polymorphism appears to have been selected for and is situated in a very exposed part of the molecule, it is likely to be of functional significance.
Gustafsson
K
K
Transplantation Biology Research Center, Massachusetts General Hospital, Boston 02129.
Germana
S
S
Sundt
T M
TM
Sachs
D H
DH
LeGuern
C
C
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics*; D003001:Cloning, Molecular; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013552:Swine; D013556:Swine, Miniature / Q000235:genetics* / Q000276:immunology*
D015704:CD4 Antigens; D009838:Oligodeoxyribonucleotides