In 1962, Mann reported an antibody which he found in the serum of a multiply transfused Caucasian male (Mr. And) that seemed to be associated with the sex of the donor red cells. In other words, the antigen frequency differed between males (XY) and females (XX) of the same race. Thus, this new antigen was named Xg^a as it appeared to be controlled by the X (sex) chromosome. The Xg antigen is well developed at birth although cord blood cells may give weaker reactions than adult cells. The Xg system, however, is unusual in that no other antigens have been identified to date. Curiously, most of the antibody producers have been males.

Biochemical analyses have shown that the Xg^a antigen is located on a 27,000 molecular weight sialoglycoprotein. This protein is encoded for by a gene on the X chromosome at position Xp22-32. The Xg locus is one of the few genes on the X chromosome that are not subject to Lyonization, ie. random "switching off" in females of one of the X genes. Goodfellow and Tippett have observed an interesting association between the Xg^a antigen and CD99. They found that the CD99 antigen also showed variable expression which appeared to be related to sex. Individuals who are high expressors of CD99 are Xg(a+). Although there are Xg(a-), CD99 low expressors, no "null phenotype" has yet to be found. Since these two proteins may associate with each other in the red cell membrane, the null would presumably lack both the Xg and CD99 proteins. No disease association has been found with a particular Xg phenotype.