Monoclonal Antibodies as Tools to Analyze the Serological and Genetic Complexities of Major Transplantation Antigens

Howard, Jonathan C.; Butcher, Geoffrey W.; Galfrè, G.; Milstein, C.; Milstein, C.

doi:10.1111/j.1600-065x.1979.tb00292.x

Cited by 121 publications

(39 citation statements)

References 36 publications

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“…A similar stretch of seven arginines is predicted for A3 n . (Table I); the low, but unambiguous, binding of R3/13 to RT1 o RBC was reported previously (22). Table I also shows results obtained with cells from BDIX rats.…”

Section: Mhc Class I Expression Cloningsupporting

confidence: 65%

A Novel Instance of Class I Modification (cim) Affecting Two of Three Rat Class I RT1-A Molecules Within One MHC Haplotype

González-Muñoz

Rolle

Brun

et al. 2003

The Journal of Immunology

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T he number of genes for MHC class I molecules varies greatly between species: from ϳ11 in pigs (1) to several thousand in the African pigmy mouse (2). Among the complement of class I genes in a species, some are designated classical class I, or MHC class Ia, genes. The protein products of the class Ia genes share certain characteristics. These include high cell surface expression levels relative to the levels of MHC class Ib genes, a major role in repertoire formation and Ag presentation for substantial numbers of ␣/␤ CD8 ϩ T lymphocytes, the ability to provoke strong cellular CD8 ϩ T cell responses in the context of allotransplantation, and a tendency toward a high degree of genetic polymorphism. MHC class I genes are found at several different positions within each MHC complex. A unifying description of mammalian MHC class I gene organization has been provided by Amadou (3), who pointed out that clusters of class I genes, varying in size from one species to another, are located at certain positions within a linear framework of conventional genes that maintains an evolutionarily conserved order.The most detailed investigations of MHC class I genetics have involved studies of this system in humans and laboratory mice. Comparative studies in other species, however, have served to stress the remarkable plasticity of this system. The description of the MHC of the laboratory rat (Rattus norvegicus) is now well advanced (4). Close scrutiny of MHC class Ia gene expression in the rat has uncovered surprising differences from its fellow murine, the mouse. 1) Rat MHC class Ia genes are all located to one side (centromeric) of the MHC class II region, i.e., there is no evidence for an H2-D or -L equivalent in the rat (the rat class Ia region is called RT1-A).2) The number of MHC class Ia genes per MHC haplotype is a variable (5, 6). Similar observations have been reported for cattle (7). 3) The TAP peptide transporter, which supplies peptides for MHC class I assembly, is functionally dimorphic in the rat (8 -10). The rat MHC class Ia system has evolved alleles that apparently take advantage of the broader peptide specificity of the rat TAP-A transporter allele, while the mouse class Ia alleles reflect a more restrictive TAP, which has properties similar to those of rat TAP-B (6, 11).The polymorphism of rat TAP described above was discovered on account of a phenomenon termed class I modification (cim).4 A rat MHC class Ia allele named RT1-A a showed striking differences in expression and antigenicity for T lymphocytes depending on the genetic origin of the MHC class II region with which it was expressed (8,12,13). It emerged that allelism of the MHC class II-linked TAP2 gene was responsible for the observations. TAP heterodimers containing the TAP2A allele could readily supply the type of peptides required for RT1-A a to assemble, but those

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Section: Mhc Class I Expression Cloningsupporting

confidence: 65%

A Novel Instance of Class I Modification (cim) Affecting Two of Three Rat Class I RT1-A Molecules Within One MHC Haplotype

González-Muñoz

Rolle

Brun

et al. 2003

The Journal of Immunology

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“…That some lines were not lysed by the monoclonal anti-H-2Kk serum may be a reflection of the peculiarities of monoclonal antibodymediated lysis, as discussed by Howard et al (29). These authors have shown that the level of antigen expression has a profound impact on the degree of lysis mediated by a particular monoclonal antibody, and this can be easily seen (54).…”

Section: Methodsmentioning

confidence: 79%

Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor.

Kerbel¹,

Lagarde²,

Dennis³

et al. 1983

Mol. Cell. Biol.

122

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Previous studies demonstrated that growth in DBA/2 mice of MDW4, a wheat germ agglutinin-resistant (WGA9 mutant of the highly metastatic MDAY-D2 DBA/2 mouse tumor, led to the emergence of WGA-sensitive (WGAS) revertants having higher ploidy levels at the site of inoculation as well as at distant visceral metastases. The results implied that MDW4 was nonmetastatic but progressed to become metastatic in vivo only after a cellular change took place which was accompanied by extinction of the WGAr phenotype and acquisition of a higher number of chromosomes. Results presented here provide strong and direct evidence for the underlying mechanism being spontaneous cell fusion in vivo between the MDW4

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“…When mixed, they acted together to give efficient lysis. Antibodies that bound to the same site failed to potentiate each other (Howard et al, 1979). These elegant experiments suggest that cytotoxic histocompatibilitytesting sera contain antibodies to more than one antigenic site on the histocompatibility antigen molecule, and so must recognize multiple differences.…”

Section: Immortalization Ofotherfunctionsmentioning

confidence: 88%

“…The screening assay must be sensitive enough to give a strong response for about l,ug of antibody/ml if concentration methods are not to be used. As discussed below, some assays do not usually work with monoclonal antibodies, for example, cytotoxicity tests (Howard et al, 1979).…”

Section: Production Of Monoclonal Antibodies Outlinementioning

confidence: 99%

“…Also, monoclonal antibodies will not usually precipitate their target antigen because they can only cross-link antigens into dimers rather than form a lattice-hence the failure of Ouchterlony assays. Classical antisera fix complement more readily than do monoclonal antibodies because complement requires at least two bound antibody molecules on neighbouring determinants (Howard et al, 1979;see below). A solution to these problems is to use suitable blends of monoclonal antibodies; for both precipitation (Jefferis et al, 1980) and cytotoxicity (Howard et al, 1979) it has been shown that a mixture of two monoclonal antibodies is sufficient.…”

Section: Special Properties Of Monoclonal Antibodiesmentioning

confidence: 99%

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Some properties and applications of monoclonal antibodies

Edwards¹

1981

Biochemical Journal

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Monoclonal Antibodies as Tools to Analyze the Serological and Genetic Complexities of Major Transplantation Antigens

Cited by 121 publications

References 36 publications

A Novel Instance of Class I Modification (cim) Affecting Two of Three Rat Class I RT1-A Molecules Within One MHC Haplotype

A Novel Instance of Class I Modification (cim) Affecting Two of Three Rat Class I RT1-A Molecules Within One MHC Haplotype

Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor.

Some properties and applications of monoclonal antibodies

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