Antibody Responses to Antigenic Determinants of Influenza Virus Hemagglutinin

Virelizier, Jean-Louis; Allison, A. C.; Schild, G. C.

doi:10.1084/jem.140.6.1571

Cited by 83 publications

(31 citation statements)

References 16 publications

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“…In this case, the antibody reacted almost exclusively with A/JAP/62 virus. This pattern of "asymmetric cross-reactivity" is not totally unexpected because type A influenza hemagglutinins possess specific determinants as well as common determinants which are shared by hemagglutinins of the same subtype (26,27). The possible relevance of this observation to the issue of CTL specificity is discussed below.…”

Section: Serologic Cross-reactivity Among Type a Influenza Viruses Ofmentioning

confidence: 93%

“…First, at least two sets of antigenic determinants are demonstrable on the type A influenza hemagglutinin molecule--specific determinants which are unique to a particular hemagglutinin and common determinants which are shared to varying degrees with hemagglutinins of the same subtype (26,27). That such sets of determinants are distinguishable is illustrated here (Table VII) where the antihemagglutinin response of BALB/c mice to A/JAP/62 virus is directed almost exclusively to that virus in spite of the high degree of cross-reactivity between this virus and the prototype A/JAP/57 virus demonstrated by other antisera.…”

Section: Discussionmentioning

confidence: 99%

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Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin.

Braciale¹

1979

The Journal of Experimental Medicine

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Because the initial realization that T cells comprised a discrete lymphocyte class, there has been a great deal of experimental work directed toward an analysis of the nature of the antigen receptor on T cells and, concomitantly, toward an assessment of the comparative specificity of T and B cells. Perhaps a major advance in understanding the molecular nature of the antigen receptor on T cells has come from studies demonstrating the expression, on the surface of specific T cells, of idiotypie determinants (immunoglobulin heavy chain variable region gene products [Vn]) 1 which are shared with the corresponding antibody (1-3). Although from such observations it might be anticipated that T cells and antibody would have comparable degrees of specificity for antigen, analyses of T-cell specificity have not necessarily fulfilled this expectation (reviewed in reference 4).A major limitation in many analyses of T-cell specificity has been the need to rely on ancillary T-cell activities, i.e., the capacity of T cells to help or suppress humoral responses or exhibit delayed-type hypersensitivity manifestations in order to assess Tcell recognition of antigen. This limitation would appear to be less severe in the case ofcytotoxic T lymphocyte (CTL) responses as antigen recognition by CTLs is directly measured by their capacity to lyse target cells expressing the appropriate antigen (5). Thus an analysis of the fine specificity of CTL recognition could provide useful information on the comparative specificities of T and B cells.Studies on the CTL response to conventional (i.e., non major histocompatibility complex [MHC] encoded) antigen have already yielded some information with regard to CTL specificity. For example, virus-specific CTLs readily distinguish target cells infected with unrelated viruses (6). Furthermore, more recent evidence along these lines suggests that distinct viral antigens are specifically recognized by CTLs (7-1 1). Perhaps more detailed information on CTL specificity has come from the analysis of the CTL response to hapten-modified cells (12)(13)(14)(15). Overall, these studies have demonstrated a high degree of specificity in CTL recognition of hapten-modified cell surfaces; however, it is not clear from these studies whether hapten per se is exclusively

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Section: Serologic Cross-reactivity Among Type a Influenza Viruses Ofmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin.

Braciale¹

1979

The Journal of Experimental Medicine

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“…Such a molecule would be expected to have multiple antigenic determinants and to date two groups of determinants have been described (Virelizier et al 1974a; Virelizier, Allison & Schild, 1974b;Laver, Downie & Webster, 1974). 52 J. S. OXFORD, G. C. SCHID, C. W. POTTER AND R. JENNINGS The HA molecules of influenza A viruses of the A/Hong Kong/68 subtype share common antigenic determinants which have been designated as crossreactive (CR) determinants (Schild et al 1974).…”

Section: Introductionmentioning

confidence: 99%

The specificity of the anti-haemagglutinin antibody response induced in man by inactivated influenza vaccines and by natural infection

Oxford

Schild

Potter

et al. 1979

J. Hyg.

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“…As a result, the response to the current strain is diminished. Over the past five decades, original antigenic sin has been observed in humans, as well as other mammals such as mice, ferrets, and rabbits (2)(3)(4)(5). This phenomenon could pose a cause for concern in the context of human immune responses to influenza vaccination programs.…”

mentioning

confidence: 99%

Strategies to alleviate original antigenic sin responses to influenza viruses

Kim

Davis

Sambhara

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

101

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Original antigenic sin is a phenomenon wherein sequential exposure to closely related influenza virus variants reduces antibody (Ab) response to novel antigenic determinants in the second strain and, consequently, impairs the development of immune memory. This could pose a risk to the development of immune memory in persons previously infected with or vaccinated against influenza. Here, we explored strategies to overcome original antigenic sin responses in mice sequentially exposed to two closely related hemagglutinin 1 neuraminidase 1 (H1N1) influenza strains A/PR/8/ 34 and A/FM/1/47. We found that dendritic cell-activating adjuvants [Bordetella pertussis toxin (PT) or CpG ODN or a squalenebased oil-in-water nanoemulsion (NE)], upon administration during the second viral exposure, completely protected mice from a lethal challenge and enhanced neutralizing-Ab titers against the second virus. Interestingly, PT and NE adjuvants when administered during the first immunization even prevented original antigenic sin in subsequent immunization without any adjuvants. As an alternative to using adjuvants, we also found that repeated immunization with the second viral strain relieved the effects of original antigenic sin. Taken together, our studies provide at least three ways of overcoming original antigenic sin.cross-reactivity | antigen presentation | memory T-cell activation

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Antibody Responses to Antigenic Determinants of Influenza Virus Hemagglutinin

Cited by 83 publications

References 16 publications

Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin.

Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin.

The specificity of the anti-haemagglutinin antibody response induced in man by inactivated influenza vaccines and by natural infection

Strategies to alleviate original antigenic sin responses to influenza viruses

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