Biomedical subjects

J J Monaco

Publications and source records attributed to J J Monaco.

59 records · Page 4Linked to original sources

PubMed1986

The LMP antigens: a stable MHC-controlled multisubunit protein complex.

In addition to encoding the well-known class I (H-2), II (Ia), and III (complement components C2, C4, and factor B) antigens, the murine MHC controls the expression of a large, intracellular protein complex of unknown function. This complex is composed of a large number of noncovalently linked low molecular weight polypeptide subunits (hence the name, LMP) which are biochemically, serologically, and genetically distinct from class I, II, and III antigens. Only two of these subunits display electrophoretic polymorphism within the standard inbred mouse strains, and both of these polymorphisms map within the H-2 complex, between the H-2K and I-A subregions. The remainder of the LMP complex subunits have not been mapped, and may be encoded elsewhere in the genome. A biochemically similar complex has been detected in human cells, although linkage to HLA remains to be established. In this article we will review the biochemistry, serology, and genetics of the LMP antigens, and will speculate on their biological function.

Alleles↗

PubMed1982

Identification of a fourth class of proteins linked to the murine major histocompatibility complex.

A series of proteins biochemically and genetically distinct from previously defined murine major histocompatibility complex class I and class II antigens is precipitated by a congeneic anti-H-2d antiserum. Sixteen such proteins have been defined, exhibiting a range of molecular weights (approximately 15,000-30,000) and isoelectric points (pI approximately 4-9). These proteins are not glycosylated, and they are probably not expressed at the cell surface. They are expressed most strongly in normal macrophages and macrophage cell lines and are also found in fibroblasts, B, T, and null cell lines. The genes controlling the expression of these proteins have been tentatively mapped within the H-2 complex, between the K and I-A subregions. Three alleles have been defined: mice of the H-2 haplotypes b and q possess a "null" allele, i.e., do not express any demonstrable protein product. Mice of the d haplotype cane be distinguished by their two-dimensional gel pattern from mice of all other positive H-2 types tested thus far (a, k, f, s, and ja).

Animals↗

PubMedDate not supplied

Molecular genetics of the K end of the murine MHC.

A systematic search of cloned DNA from the region between the Pb (A beta 3) and Ob (A beta 2) genes of the murine major histocompatibility complex (MHC) has revealed the presence of at least seven new genes. Three of these genes show significant similarity to MHC class II antigens. Two of the other genes are members of a superfamily of transport protein genes and are believed to function in the transport of antigenic peptides during antigen processing. Genes encoding at least two subunits of a large intracellular protein complex (the LMP complex) that is believed to be involved in antigen processing were previously mapped to the same genetic region. This data suggests that this region of the MHC contains, in addition to MHC class I and class II genes whose products provide the scaffolding for antigen presentation, a cluster of genes required for antigen processing.

Animals↗

PubMedDate not supplied

H-2-linked low-molecular weight polypeptide antigens assemble into an unusual macromolecular complex.

The major histocompatibility complex (MHC) is a cluster of tightly linked genes whose products are of central importance in the functioning of the immune system. Class I and II MHC antigens are integral membrane proteins which regulate cell-surface interactions between T cells and their targets, while class III antigens are components of the complement system of serum proteins. All available evidence indicates that the structure and function of the MHC and its gene products are highly conserved among species (for review, see ref.5). We recently reported the existence in murine cells of a fourth class of MHC-linked polypeptides which are biochemically and genetically distinct from previously identified MHC gene products: BALB.B anti-BALB/c (anti-H-2d) antiserum immunoprecipitates a set of 16 cytoplasmic low-molecular weight polypeptides (LMP) from BALB/c spleen cells and from the WEHI-3 cell line. The production of these peptides is coordinately regulated (by immune interferon) with the production of the class I and II MHC antigens, suggesting that they too are functionally relevant to the immune system. We demonstrate here that these 16 polypeptides are associated with one another in vivo as a very large (580,000-molecular weight, Mr) noncovalent complex. The unusual nature of this complex has allowed the non-immunochemical identification of similar complexes from (serologically negative) H-2b murine cells and from a human cell line. Thus, LMP antigens display two properties in common with other MHC antigens: they are both polymorphic and genetically conserved across species.

Animals↗

PubMedDate not supplied

MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters.

The T-cell immune response is directed against antigenic peptide fragments generated in intracellular compartments, the cytosol or the endocytic system. Peptides derived from cytosolic proteins, usually of biosynthetic origin, are presented efficiently to T-cell receptors by major histocompatibility complex (MHC) class I molecules, with which they assemble, probably in the endoplasmic reticulum (ER). In the absence of recognizable N-terminal signal sequences, such cytosolic peptides must be translocated across the ER membrane by a novel mechanism. Genes apparently involved in the normal assembly and transport of class I molecules may themselves be encoded in the MHC. Here we show that one of these, the rat cim gene, maps to a highly polymorphic part of the MHC class II region encoding two novel members of the family of transmembrane transporters related to multidrug resistance. Other members of this family of transporter proteins are known to be capable of transporting proteins and peptides across membranes independently of the classical secretory pathway. Such molecules are credible candidates for peptide pumps that move fragments of antigenic proteins from the cytosol into the ER.

Amino Acid Sequence↗