Molecular localization of human class II MT2 and MT3 determinants.

Abstract

The antigens encoded in the HLA-D region of the human major histocompatibility complex (MHC) 1 were originally defined with homozygous typing cells by mixed leukocyte culture and, subsequently, by use of human alloantisera reacting with antigens selectively expressed on B cells (1, 2). These antigens were later shown to be the human equivalents of the murine Ia molecules. The major serologically defined specificities, called DR, were found to be closely associated with the specificities defined by HTCs. Later, the development of ailoantisera permitted identification of additional serologic specificities such as DC, MB, MT, and Te (3-8) which are not associated with a single DR specificity but, instead, are found associated with two or more DR alleles and are, therefore, called supertypic. For example, MT2 is usually found on DR3-, DR5-, DRw6-, or DRw8-bearing cells while MT3 is usually found on cells from DR4-, DR7-, or DRwg-positive donors. The apparent equivalence of terms used by different investigators is shown in Table I (see also reference 3).Studies of the structural bases for these serological specificities have focused on three types of molecules that have been described biochemically. In a total Ia isolate, DR molecules are the predominant set of HLA-D region antigens and are homologues of the murine I-E molecules (9). These molecules bear the DR serologic specificities, which have been shown to be associated with their polymorphic beta chains (9). A DR homozygous cell line expresses DR molecules that are a set of closely related proteins which appear to share a single alpha chain and possess several structurally distinct beta chains (10, 1 1). It is not clear if all of these 1-E-like species carry the DR serologic determinants that are defined with alloantisera. The DS (DC) antigens are homologues of the murine I-A antigens (12) and bear the MB serologic determinants (13,14).

Definition of a possible genetic basis for susceptibility to acute myelogenous leukemia associated with the presence of a polymorphic Ia epitope.

“…As shown in Table I, the monoclonal antibody l09d6 reacted with an epitope expressed on the blasts found in 85% of 77 acute myelogenous leukemia patients but only in 40.5% of controls, relative risk (RR) = +7.88, population attributable risk (b) = 0.75, P < 0.000005 (uncorrected). In a healthy caucasian control population, the molecule bearing the l09d6 determinant is usually found in association with the HLA DRw53 allospecificity determined by polyclonal typing reagents, r = 0.724 (20), but in the leukemic group the frequency of HLA DRw53 was slightly, but not significantly, increased. In the control Caucasian population, the presence of the 17-3-3S determinant is associated with the presence ofthe l09d6 determinant, r = 0.783.…”

“…Both chains of the Ia molecules are encoded by genes found in three subregions: DR, DQ (DC or DS), and DP (SB) (20). Two polymorphic O-chain sequences and one nonpolymorphic a-chain are thought to be encoded in the DR subregion, while the more centromeric DQ subregion contains two pairs of polymorphic a-chain and 0-chain genes; the DP subregion is similarly organized (21)(22)(23)(24)(25).…”

Differential Expression of DRw52‐Like Determinants Detected by Monoclonal Antibodies

“…Although these latter MoAb thus appear to have an identical specificity, several investigators have demonstrated that they are detecting different determinants. Binding of the I-LR2 MoAb can be inhibited by preincubation with the 7.3.19.1 MoAb on DR3+ cells but not on DR5+cells [3], whereas I-LR2and7. 3.19.1 react with mutually exclusive subsets of DR-like molecules on DR5+ and DRw6+ cells [4].…”

DNA and Protein Studies of HLA Class II Molecules: Their Relationship to T Cell Recognition

“…DR family-associated Ia determinants can be divided into two series based on their population distributions; recent evidence potentially relates them to different aO diners of DR. The DRI thru DRwl4 specificities are thought to be associated with one of the DR dimers, arbitrarily aBi, whereas as the DRy52 and DRw53 (previously referred to as MT2 and MT3) specificities are thought to be related to an Ci2 diner (Hurley et al, 1984). Although the associations with a81 have been examined for only certain of the DRl thru DRwl4 antigens, and there should therefore be some hesitation in accepting these assignments too firmly, we shall use this concept in the article.…”