A SINGLE AMINO-ACID SUBSTITUTION IN A COMMON AFRICAN ALLELE OF THE CD4 MOLECULE ABLATES BINDING OF THE MONOCLONAL-ANTIBODY, OKT4

作者：LEDERMAN S^*; DEMARTINO JA; DAUGHERTY BL; FOELDVARI I; YELLIN MJ; CLEARY AM; BERKOWITZ N; LOWY I; BRAUNSTEIN NS; MARK GE; CHESS L

来源：Molecular Immunology, 1991, 28(11): 1171-1181.

DOI：10.1016/0161-5890(91)90003-3

The CD4 molecule is a relatively non-polymorphic 55 kDa glycoprotein expressed on a subset of T lymphocytes. A common African allele of CD4 has been identified by non-reactivity with the monoclonal antibody, OKT4. The genetic basis for the OKT4- polymorphism of CD4 is unknown. In the present paper, the structure of the CD4 molecule from an homozygous CD4OKT4- individual was characterized at the molecular level. The size of the CD4OKT4- protein and mRNA were indistinguishable from those of the OKT4+ allele. The polymerase chain reaction (PCR) was used to map the structure of CD4OKT4- cDNAs by amplifying overlapping DNA segments and to obtain partial nucleotide sequence after asymmetric amplification. PCR was then used to clone CD4OKT4- cDNAs spanning the coding region of the entire, mature CD4 protein by amplification of two overlapping segments followed by PCR recombination. The nucleotide sequence of CD4OKT4- cDNA clones revealed a G --> A transition at bp 867 encoding an arginine --> tryptophan substitution at amino acid 240 relative to CD4OKT4+. Expression of a CD4OKT4- cDNA containing only this transition, confirmed that the arginine --> tryptophan substitution at amino acid 240 ablates the binding of the mAb OKT4. A positively charged amino acid residue at this position is found in chimpanzee, rhesus macaque, mouse and rat CD4 suggesting that this mutation may confer unique functional properties to the CD4OKT4+ protein.

• 出版日期1991-11