The Privacy of T Cell Memory to Viruses

Welsh, Raymond M.; Kim, Sung-Kwon; Cornberg, Markus; Clute, Shalyn Catherine; Selin, Liisa K.; Naumov, Yuri N.

doi:10.1007/3-540-32636-7_5

Cited by 31 publications

(37 citation statements)

References 148 publications

(203 reference statements)

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“…3), in which a CD4 ϩ T cell clone recognizes self-HLA plus vaccinia peptide, and also allogeneic cells. This demonstrates that vaccinia-specific T cells can show promiscuous APC recognition, typical of many virus-specific T cells (86,87). Self-reactive T cells are not entirely eliminated during development (88), and it is possible that CD4 T cells reactive with vaccinia epitopes could also cross-react with self-HLA and peptides derived from cellular proteins.…”

Section: Discussionmentioning

confidence: 94%

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Jing¹,

Chong

Byrd³

et al. 2007

The Journal of Immunology

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Vaccination with replication-competent vaccinia protects against heterologous orthopoxvirus challenge. CD4 T cells have essential roles helping functionally important Ab and CD8 antiviral responses, and contribute to the durability of vaccinia-specific memory. Little is known about the specificity, diversity, or dominance hierarchy of orthopoxvirus-specific CD4 T cell responses. We interrogated vaccinia-reactive CD4 in vitro T cell lines with vaccinia protein fragments expressed from an unbiased genomic library, and also with a panel of membrane proteins. CD4 T cells from three primary vaccinees reacted with 44 separate antigenic regions in 35 vaccinia proteins, recognizing 8 to 20 proteins per person. The integrated responses to the Ags that we defined accounted for 49 to 81% of the CD4 reactivity to whole vaccinia Ag. Individual dominant Ags drove up to 30% of the total response. The gene F11L-encoded protein was immunodominant in two of three subjects and is fragmented in a replication-incompetent vaccine candidate. The presence of protein in virions was strongly associated with CD4 antigenicity. These findings are consistent with models in which exogenous Ag drives CD4 immunodominance, and provides tools to investigate the relationship between Ab and CD4 T cell specificity for complex pathogens.

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Section: Discussionmentioning

confidence: 94%

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Jing¹,

Chong

Byrd³

et al. 2007

The Journal of Immunology

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“…[24][25][26][27][28][29][30][31][32][33][34][48][49][50][51][52][53] For example, in the C57BL/6 mouse (H2 b ), CD8 T cell crossreactive epitopes have been defined between LCMV and Pichinde virus (PICV), LCMV and vaccinia virus (VACV), LCMV and murine cytomegalovirus (MCMV), LCMV and IAV, IAV and MCMV, and PICV and VACV, and complex networks of mouse or human T cell crossreactivity can exist between two viruses. 23,24,27,28,34,[54][55][56] Furthermore, structural studies on crossreactivity between LCMV and VACV epitopes can pinpoint the target of crossreactivity and render the OVA SIINFEKL epitope crossreactive with LCMV by an amino acid substitution. 57,58 Crossreactivity is an essential feature of TCR, and the positive selection of T cells in the thymus is mediated through self-peptides that crossreact with a substantial repertoire of foreign epitopes.…”

Section: Heterologous Immunity and T Cell Crossreactivitymentioning

confidence: 99%

“…The hierarchy of T cell responses to immunodominant epitopes in immunologically naive genetically identical mice is very consistent, [53][54][55][56] but the amino acid sequences of the TCRs responding to these epitopes differ from mouse to mouse; these are sometimes called 'private' specificities. [57][58][59][60] In a T cell repertoire, that which is common between individuals, be it TCR VA usage or a common amino acid sequence or 'motif', is a public specificity; that which is different between individuals, such as a CDR3 sequence, is a 'private' specificity.…”

Section: Heterologous Immunity and T Cell Crossreactivitymentioning

confidence: 99%

“…50,61,62 The private specificity of TCR repertoires in the memory pool has an impact on heterologous immunity, where subsets of a crossreactive T cell repertoire are mobilized to control the heterologous viral infection. [31][32][33]56 Studies revealing 'private specificities' of T cell responses showed that if memory cells from one LCMV-immune mouse were adoptively transferred into three naive congenic recipients later challenged with heterologous viruses, those three mice showed a similar epitope hierarchy as the original donor and differed from that of a set that received cells from an alternate donor. 32 In vivo findings in mice showed that a high affinity crossreactive response between LCMV and PICV would lead to narrowing of the TCR repertoire during the heterologous infection.…”

Section: Heterologous Immunity and T Cell Crossreactivitymentioning

confidence: 99%

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Vaccination and heterologous immunity: educating the immune system

Gil¹,

Kenney²,

Mishra³

et al. 2015

Transactions of the Royal Society of Tropical Medicine and Hygiene

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This review discusses three inter-related topics: (1) the immaturity of the neonatal and infant immune response; (2) heterologous immunity, where prior infection history with unrelated pathogens alters disease outcome resulting in either enhanced protective immunity or increased immunopathology to new infections, and (3) epidemiological human vaccine studies that demonstrate vaccines can have beneficial or detrimental effects on subsequent unrelated infections. The results from the epidemiological and heterologous immunity studies suggest that the immune system has tremendous plasticity and that each new infection or vaccine that an individual is exposed to during a lifetime will potentially alter the dynamics of their immune system. It also suggests that each new infection or vaccine that an infant receives is not only perturbing the immune system but is educating the immune system and laying down the foundation for all subsequent responses. This leads to the question, is there an optimum way to educate the immune system? Should this be taken into consideration in our vaccination protocols?

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“…This is caused in part by the "private specificities" of unique T cell repertoires generated by random DNA recombination events even in genetically identical hosts. 6,7 Mouse studies have shown that such variation can even occur in genetically identical individuals subjected to similar infection histories. In syngeneic LCMV-immune mice challenged with VV, T cell immunodominance, and cross-reactivity patterns vary, such that, for example, in some mice VV selectively expands T cells cross-reactive with the LCMV epitope NP205-212, whereas in other mice there is selective expansion of T cells specific to GP34-41 or to GP118-125.…”

Section: Heterologous Immunity Associated With Cross-reactive T-cell mentioning

confidence: 99%

Pathological Features of Heterologous Immunity Are Regulated by the Private Specificities of the Immune Repertoire

Nie

Lin

Kim

et al. 2010

The American Journal of Pathology

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Heterologous immunity associated with cross-reactive T-cell responses is proposed to contribute to variations among individuals in the pathogenesisA number of studies have shown that T cell responses to viral infections may be influenced by memory T cells generated in response to unrelated pathogens. [1][2][3][4][5] This alteration in responses is displayed by changes in T cell immunodominance hierarchies, 1 by alterations in viral loads and protective immunity, and by marked changes in immunopathology. 2,4 This "heterologous immunity" can be a consequence of unanticipated T cell cross-reactivity between different pathogens. Indeed, T cell specificity can be quite degenerate, and cross-reactivity between different viruses is common. For example, human studies have revealed strong T cell cross-reactivity between influenza A virus (IAV) and Epstein-Barr virus (EBV) epitopes and between IAV and hepatitis C virus (HCV) epitopes. Acute infectious mononucleosis and fulminant hepatitis have been suggested as pathological manifestations of such CD8 T cell cross-reactivity. 3,5 Heterologous immunity can best be studied and manipulated in mouse model systems, and C57BL/6 mice immune to lymphocytic choriomeningitis virus (LCMV) and subsequently challenged with vaccinia virus (VV) show enhanced protective immunity and altered immunopathology, in contrast to naïve mice infected with VV.2,4 These are manifestations of heterologous immunity that can be duplicated by transfer of LCMV-immune T cell populations into naïve mice, followed by challenge with VV. VV challenge of LCMV-immune mice by the i.p. route results in a severe panniculitis, or inflammation of visceral fat, with pathology similar to that of human erythema nodosum. The fat tissue is infiltrated with T cells crossreactive between LCMV and VV, and the pathology is dependent on interferon-␥ (IFN-␥). VV challenge of LCMVimmune mice by the intranasal route results in abnormally pronounced T cell infiltrates in the lungs, sometimes with the accompanying pathology known as bronchiolitis obliterans.A property of heterologous immunity noted both in the human and murine systems is that there can be dramatic variation in pathogenesis and in the cross-reactive specSupported by NIH grant AI-46578 (L.K.S.), AI-46629 (L.K.S.), and AR35506 (R.M.W.) and DR-32520.

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The Privacy of T Cell Memory to Viruses

Cited by 31 publications

References 148 publications

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

Vaccination and heterologous immunity: educating the immune system

Pathological Features of Heterologous Immunity Are Regulated by the Private Specificities of the Immune Repertoire

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