HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in Western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy

Stam, Nico J.; Vroom, Thea M.; Peters, Paul J.; Pastoors, E. B.; Ploegh, Hidde L.

doi:10.1093/intimm/2.2.113

Cited by 238 publications

(175 citation statements)

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“…However, when only analysing complete loss of MHC-I expression the percentage of carcinomas showing MHC-I alterations observed using HCIO and RaHC (48%) was considerably higher than obtained with W6/32 (9%) by Connor & Stern (1990). The monoclonal antibody W6/32 recognises MHC-I heavy chains, complexed with P2-microglobulin, and is reactive only on frozen tissue, whereas HCIO and RaHC used in our study recognise MHC-I heavy chain antigens both in frozen and paraffin embedded tissue (Stam et al, 1990 Changes in MHC-II expression were detected as well in a substantial number of CIN lesions and cervical carcinomas. MHC-II upregulation on epithelial cells could enhance tumor-specific immunity by bypassing the classical antigen presenting cell (APC) mediated route and directly presenting antigen in the context of MHC-II to T-helper cells (OstrandRosenberg et al, 1991).…”

Section: Mhc Class I and Ii Expressioncontrasting

confidence: 58%

Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions

Cromme

Meijer²,

Snijders³

et al. 1993

Br J Cancer

110

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Summary Cervical intraepithelial neoplasia (CIN) grades I to III lesions (n = 94) and squamous cell carcinomas of the uterine cervix (n = 27) were analysed for MHC class I and II expression and presence of HPV genotypes.MHC class I and II expression was studied by immunohistochemistry and HPV typing was performed by general primer-and type-specific primer mediated PCR (GP/TS PCR). Both A central role in the antigen-specific immune response is played by the major histocompatibility complex (MHC), which are cell surface proteins that act as restricting elements in the recognition of antigen by T-cells. MHC class I (MHC-I) present endogenous antigen to cytotoxic T-lymphocytes (CTLs). Low levels or lack of MHC-I surface expression can consequently render aberrant cells non-immunogenic to CTLs, and may provide a way for cells to escape immune surveillance. MHC-1 alterations have been described in human cancer of different sites of the body (see review RuizCabello et al., 1991).Generally, MHC class II (MHC-II) surface expression is restricted to specialised antigen presenting cells (APCs), that present mainly opsonised exogenous antigen to T-helper cells. Recognition leads to activated T-cells, which can stimulate B-cell, CTL proliferation and MHC non-restricted killing by natural killer (NK) cells or activated macrophages. Occasionally, other cells like neoplastic epithelial cells have been described to express MHC-II, which could assist in the onset of the cellular immune response (Ostrand-Rosenberg et al., 1991).Infections with specific human papillomavirus (HPV) types are strongly associated with the development of cervical cancer, with HPV types 16 and 18 as the most predominant types (Zur Hausen, 1989 (Connor & Stern, 1990;Glew et al., 1992), suggesting that changes in the presentation of viral tumour antigens to the cellular immune system can occur. However, to get insight whether altered MHC-I and -II expression is related to the development of cervical cancer from its premalignant lesions, it is necessary to study dysplastic cervical lesions (CIN) for the MHC-I and -II status.Tumour virus based mechanisms have been described that specifically influence MHC-I cell surface expression (Signas et al., 1982;Schrier et al., 1983). Similar mechanisms could exist for HPV affecting antigen presentation of the infected cells. However, little is known about MHC alterations in CIN lesions in relation to the presence of different HPV genotypes.Therefore in this study expression of MHC-I and -II was investigated in CIN lesions of different grades and cervical carcinomas. HPV typing was carried out by a combined general primer-mediated (GP-) and type-specific (TS-) polymerase chain reaction (PCR) strategy (van den Brule et al., 1991;Walboomers et al., 1992). In addition, HPV RNA in situ hybridisation (RISH) was applied to some HPV 16 PCR positive lesions, in order to localise cells containing transcriptionally active HPV 16 in relation to altered MHC expression. The results indicate that MHC-I and -II alterations are also...

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Section: Mhc Class I and Ii Expressioncontrasting

confidence: 58%

Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions

Cromme

Meijer²,

Snijders³

et al. 1993

Br J Cancer

110

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“…mAb HCA2 (a kind gift from H. Ploegh, Harvard Medical School, Boston, MA) recognizes unfolded A2 molecules (35) and was used for immunoblots. Open/peptide-empty conformers of human MHC-I molecules or SCT constructs were also detected by mAb 64-3-7 epitope-tagging (28 -32).…”

Section: Methodsmentioning

confidence: 99%

Human Major Histocompatibility Complex (MHC) Class I Molecules with Disulfide Traps Secure Disease-related Antigenic Peptides and Exclude Competitor Peptides

Truscott

Wang

Lybarger

et al. 2008

Journal of Biological Chemistry

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The ongoing discovery of disease-associated epitopes detected by CD8 T cells greatly facilitates peptide-based vaccine approaches and the construction of multimeric soluble recombinant proteins (e.g. tetramers) for isolation and enumeration of antigen-specific CD8 T cells. Related to these outcomes of epitope discovery is the recent demonstration that MHC class I/peptide complexes can be expressed as single chain trimers (SCTs) with peptide, ␤ 2 m and heavy chain connected by linkers to form a single polypeptide chain. Studies using clinically relevant mouse models of human disease have shown that SCTs expressed by DNA vaccination are potent stimulators of cytotoxic T lymphocytes. Their vaccine efficacy has been attributed to the fact that SCTs contain a preprocessed and preloaded peptide that is stably displayed on the cell surface. Although SCTs of HLA class I/peptide complexes have been previously reported, they have not been characterized for biochemical stability or susceptibility to exogenous peptide binding. Here we demonstrate that human SCTs remain almost exclusively intact when expressed in cells and can incorporate a disulfide trap that dramatically excludes the binding of exogenous peptides. The mechanistic and practical applications of these findings for vaccine development and T cell isolation/enumeration are discussed.

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“…The expression of HLA-A [HC-A2, mouse monoclonal antibody (MAb), 1:500 (Stam et al, 1990)], HLA-B/C [mouse MAb HC-l0, 1:1000 (Stam et al, 1990) (Kummer et al, 1993] were analysed as described previously (Sale et al, 1994;Cromme et al, 1995).…”

Section: Immunohistochemistry Monostainingmentioning

confidence: 99%

Assessment of cytotoxic T-lymphocyte phenotype using the specific markers granzyme B and TIA-1 in cervical neoplastic lesions

Bontkes

Gruijl²,

Walboomers³

et al. 1997

Br J Cancer

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HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in Western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy

Cited by 238 publications

References 0 publications

Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions

Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions

Human Major Histocompatibility Complex (MHC) Class I Molecules with Disulfide Traps Secure Disease-related Antigenic Peptides and Exclude Competitor Peptides

Assessment of cytotoxic T-lymphocyte phenotype using the specific markers granzyme B and TIA-1 in cervical neoplastic lesions

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