Specificity studies on cytotoxic thymus-derived lymphocytes reactive with influenza virus-infected cells: evidence for dual recognition of H-2 and viral hemagglutinin antigens.

The host defense response to influenza infection is complex. Specific humoral antibodies develop to the strain-specific surface antigens, the hemagglutinin and the neuraminidase, and to the internal antigens (matrix and nucleoprotein) which are common to all influenza A viruses (1). Antibodies to the hemagglutinin, which is the major surface antigen, neutralize viral infectivity (2). In addition to antibodies which have been detected against virion antigens, a cytotoxic T-cell response with specificity against the viral hemagglutinin on influenza-infected target cells (3-5) has been recently described. A more cross-reactive cytotoxic T-cell response has also been observed when a nonpermissively infected target cell is used in cytotoxicity assays (6,7). The present report describes the development during influenza infection and after vaccination of a cytolytic humoral antibody response which is directed against the hemagglutinin on infected target cells. This antibody-mediated lysis of infected cells in complement dependent, as has been reported with other virus infections (8-11).

Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Hemagglutinin-specific complement-dependent antibody response to influenza infection

Verbonitz¹,

Ennis²,

Hicks³

et al. 1978

“…94% of the antibodies that bound PR8 in the context of L929 cells were also capable of binding PR8 in the context of BALB.K kidney fibroblasts. Because primary kidney cells, unlike L929 cells, are capable of supporting a productive influenza infection (21), the reactivity of these antibodies with infected BALB.K kidney fibroblasts demonstrates that the vast majority of antibodies recognizing only infected cells are not recognizing PR8 determinants unique to the L929 tumor cell, nor determinants expressed only on nonproductively infected cells. A similar analysis was carried out with nonimmune C57BL/10 B cells (H-2 ~) responsive to syngeneie PR8-infected EL-4 cells.…”

Section: The Frequency Of Monoclonal Responses Restricted To Pr8-infementioning

confidence: 99%

Participation of the major histocompatibility complex in antibody recognition of viral antigens expressed on infected cells.

Wylie¹,

Sherman²,

Klinman³

1982

The capacity of the antibody repertoire to recognize complex antigens on viral-infected cells was investigated at the level of monoclonal B cell responses. A majority of primary B cells responsive to PR8(H1N1)-infected H-2 syngeneic cells produced antibody that bound viral determinants only in the context of infected cells and not the isolated virion. An examination of the fine specificity of such antibodies revealed that most could be distinguished by a panel of cells infected with closely related heterologous H1 influenza strains. Indeed, most antibodies bound hemagglutinin determinants of PR8 exclusively, and few were broadly cross-reactive. An examination of the same antibodies for their recognition of cell surface antigens revealed that the majority recognized MHC-encoded antigenic determinants. Thus, most BALB.K (H-2k) primary B cells responsive to PR8-L919 (H-2k) cells produced monoclonal antibodies that bound PR8-antigens only in the context of H-2Dk-infected cells. Most C57BL/10 (H-2b) B cells responsive to PR8-EL4 (H-2b) cells produced monoclonal antibodies that bound PR8 antigens only in the context of H-2Kb-infected cells. These latter antibodies were further shown to recognize that H-2Kb molecule by virtue of their capacity to be discriminated by a panel of PR8-infected H-2Kb mutant cells. These findings demonstrate that much of the antibody repertoire is capable of highly specific complex recognition of viral antigenic determinants in the context of the appropriate MHC alloantigen.

“…Thus H.2K and/or H-2D compatibility between cytotoxic T lymphocyte and virus-infected target cell is generally required for immune lysis to occur (6)(7)(8)(9)(10). Evidence has recently been reported which strongly favors the notion that cytotoxic T-lymphocyte recognition of MHC-coded antigens occurs independently from recognition of viral antigens (25). The phenomenon of MHC-restricted lysis of viral-infected target cells is relevant to a consideration of whether immune surveillance occurs against altered MHC-coded antigens of tumors.…”

Section: Discussionmentioning

confidence: 99%

Lung tumor-associated derepressed alloantigen coded for by the K region of the H-2 major histocompatibility complex

Gipson¹,

Imamura²,

Conliffe³

et al. 1978

Transplacental induction of lung tumors in C3HfeB/HeN (C3Hf) strain mice can be readily achieved with the carcinogen 1-ethyl-1-nitrosourea. Several of these tumors express, as a tumor-associated transplantation antigen (TATA), a normal tissue alloantigen present in strain A and C3H/HeN (C3H) mice. In the present study it was shown that the tumor-associated alloantigen on the C3Hf-derived lung tumor 85 was present in all mice of H-2(a) and H-2(k) haplotypes tested and in CBA (532) strain mice (H-2(ka) haplotype). Studies using congenic-resistant and recombinant strains of mice indicated that the genetic locus controlling the expression of this antigen was either within or to the left of the H-2K region of the major histocompatibility complex (MHC). Thus the antigen was expressed in B10.A (4R) mice (kkbbbb MHC haplotype) but not in B10 (bbbbbb) or B10.AQR mice (qkkddd). The antigen was expressed in all tissues tested of C3H and A strain mice. It was not detected on any tissue tested including embryo tissue of C3Hf mice or mice of MHC haplotype other than H-2(k) or H-2(a). Because C3Hf strain mice were originally derived from C3H strain mice (H-2(k)), the MHC haplotype of C3Hf mice has been provisionally designated H-2(kb). The finding of a tumor-associated change in the expression of a H-2K region-coded antigen is consistent with the concept that MHC-coded antigens may act as targets for immunological surveillance of tumors.