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At least 19 recordsLinked to original sources
PubMed2026

TCRspec: A Recognition Interface-Informed Multimodal Method for TCR-pMHC Specificity Prediction.

Specific recognition between T-cell receptors (TCRs) and peptide-major histocompatibility complexes (pMHCs) is central to adaptive immunity, yet accurate prediction of TCR-pMHC specificity remains challenging. Existing models mainly rely on sequence features or isolated molecular structures, limiting their ability to capture interface-level determinants within the ternary recognition complex. Here, we constructed the multimodal TCR-pMHC ternary complex (MM-TCR) data set, integrating paired TCR-pMHC sequences, V/J gene annotations, and modeled TCR-pMHC complex structures refined by short molecular dynamics-based relaxation. Based on MM-TCR, we developed TCRspec, an interpretable multimodal framework combining sequence embeddings, gene-usage features, and complex-level structural representations. Under a stringent CD-HIT TCR-cluster-disjoint split, TCRspec achieved an average AUROC of 0.896 and AUPRC of 0.882 across seven antigen-specific test data sets, outperforming representative baseline models. Cross-validation and ablation analyses confirmed the contribution of ternary complex structural information and MD-refined structures. In independent OOD peptide-TCR systems, TCRspec retained discriminative performance and identified model-inferred peptide positions associated with TCR recognition, providing a structure-informed framework for TCR specificity prediction.

Receptors, Antigen, T-Cell↗
PubMed2025

Assessing data size requirements for training generalizable sequence-based TCR specificity models via pan-allelic MHC-I point-mutation ligandome evaluation.

Rapid identification of T cell receptors (TCRs) that specifically bind patient-unique neoepitopes is a critical challenge for personalized TCR-based therapies in oncology. Due to enormous diversity of both TCR and neoepitope repertoires, a machine learning predictor of TCR-pMHC specificity for personalized therapy must generalize to TCRs and epitopes not seen in the training data. We estimate the necessary size of such training data. We first confirm that published models fail to generalize beyond a single-residue dissimilarity to the epitope training set distribution. We then impute the point-mutation ligandome across the 34 most prevalent human MHC alleles and represent it as a graph based on our established dissimilarity cutoff. By finding the dominating set of this graph, we estimate that between one and 100 million epitopes are required to train a generalizable sequence-based TCR specificity prediction model-1000 times the size of current public data.

Humans↗
PubMed2000

Nondeletional T-cell receptor transgenic mice: model for the CD4(+) T-cell repertoire in chronic hepatitis B virus infection.

Chronicity after infection with the hepatitis B virus (HBV) can occur for a variety of reasons. However, once established, chronicity may be maintained by high levels of viral proteins circulating in the serum. To examine the characteristics of T cells capable of coexisting with the secreted hepatitis B e antigen (HBeAg), T-cell receptor (TCR) transgenic (Tg) mice were produced. To ensure that HBeAg-specific T cells would not be deleted in the presence of serum HBeAg, the TCR alpha- and beta-chain genes used to produce the TCR-Tg mice were derived from T-cell hybridomas produced from immunizing HBeAg-Tg mice. A TCR-Tg lineage (11/4-12) was produced that possessed a high frequency ( approximately 67%) of CD4(+) T cells that expressed a Tg TCR specific for the HBeAg. As predicted, when 11/4-12 TCR-Tg mice were bred with HBeAg-Tg mice no deletion of the HBeAg-specific CD4(+) T cells occurred in the thymus or the spleen. Functional analysis of the TCR-Tg T cells revealed that the HBeAg-specific CD4(+) T cells escaped deletion in the thymus and periphery by virtue of low avidity. Regardless of their low avidity, HBeAg-specific TCR-Tg T cells could be activated by exogenous HBeAg, as measured by cytokine production in vitro and T-helper-cell function for anti-HBe antibody production in vitro and in vivo. Furthermore, activated TCR-Tg HBeAg-specific T cells polarized to the Th1 subset were able to elicit liver injury when transferred into HBeAg or HBcAg-Tg recipients. Therefore, HBeAg-specific CD4(+) T cells that can survive deletion or anergy in the presence of circulating HBeAg nonetheless are capable of being activated and of mediating liver injury in vivo. The 11/4-12 TCR-Tg lineage may serve as a monoclonal model for the HBe/HBcAg-specific CD4(+) T-cell repertoire present in chronically infected HBV patients.

Adoptive Transfer↗
PubMed1995

Predicted complementarity determining regions of the T cell antigen receptor determine antigen specificity.

The antigen receptor on T cells (TCR) has been predicted to have a structure similar to a membrane-anchored form of an immunoglobulin F(ab) fragment. Virtually all of the conserved amino acids that are important for inter- and intramolecular interactions in the VH-VL pair are also conserved in the TCR V alpha and V beta chains. A molecular model of the TCR has been constructed by homology and we have used the information from this, as well as the earlier structural predictions of others, to study the basis for specificity. Specifically, regions of a TCR cloned from an antigen-specific T cell were stitched into the corresponding framework of a second TCR. Results indicate that the substitution of amino acid sequences corresponding to the complementarity determining regions (CDRs) of immunoglobulin can convey the specificity for antigen and major histocompatibility complex molecules. These data are consistent with a role, but not an exclusive role, for CDR3 in antigen peptide recognition.

Amino Acid Sequence↗
PubMed2025

Learning predictive signatures of HLA type from T-cell repertoires.

T cells recognize a wide range of pathogens using surface receptors that interact directly with peptides presented on major histocompatibility complexes (MHC) encoded by the HLA loci in humans. Understanding the association between T cell receptors (TCR) and HLA alleles is an important step towards predicting TCR-antigen specificity from sequences. Here we analyze the TCR alpha and beta repertoires of large cohorts of HLA-typed donors to systematically infer such associations, by looking for overrepresentation of TCRs in individuals with a common allele.TCRs, associated with a specific HLA allele, exhibit sequence similarities that suggest prior antigen exposure. Immune repertoire sequencing has produced large numbers of datasets, however the HLA type of the corresponding donors is rarely available. Using our TCR-HLA associations, we trained a computational model to predict the HLA type of individuals from their TCR repertoire alone. We propose an iterative procedure to refine this model by using data from large cohorts of untyped individuals, by recursively typing them using the model itself. The resulting model shows good predictive performance, even for relatively rare HLA alleles.

Humans↗
PubMed2001

Modeling the T-helper cell response in acute and chronic hepatitis B virus infection using T-cell receptor transgenic mice.

Chronicity following hepatitis B virus (HBV) infection may be maintained by high levels of viral proteins circulating in the serum. To examine the characteristics of T cells capable of co-existing with the secreted hepatitis B e-antigen (HBeAg), T-cell receptor (TCR) transgenic (Tg) mice were produced. To insure that HBeAg-specific T cells would not be deleted in the presence of serum HBeAg, the TCR alpha and beta-chain genes used to produce the TCR-Tg mice were derived from T-cell hybridomas from HBeAg-Tg mice. A TCR-Tg lineage (11/4-12) was produced that possessed a high frequency (approximately 67%) of CD4(+) T cells that expressed a TCR-Tg specific for the HBeAg. As predicted, when 11/4-12 TCR-Tg mice were bred with HBeAg-Tg mice no deletion of the HBeAg-specific CD4(+) T cells occurred in the thymus or the spleen. Functional analysis of the TCR-Tg T cells revealed that the HBeAg-specific CD4(+) T cells escaped deletion in the thymus and periphery by virtue of low avidity. Regardless of their low avidity, HBeAg-specific TCR-Tg T cells could be activated by exogenous HBeAg as measured by cytokine production in vitro and T-helper cell function for anti-HBe antibody production in vitro and in vivo. Furthermore, activated TCR-Tg HBeAg-specific T cells polarized to the Th(1) subset were able to elicit liver injury when transferred into HBeAg or HBcAg-Tg recipients. Therefore, HBeAg-specific CD4(+) T cells that can survive deletion or anergy in the presence of circulating HBeAg nonetheless are capable of being activated and of mediating liver injury in vivo.

Adoptive Transfer↗
PubMed1994

Identification of two V beta 7-specific viral superantigens.

The commonly used strains of laboratory mice have mouse mammary tumor viruses (MTV) integrated at various locations in their DNA. The number and position of these integrants varies from one strain of mouse to another. It has recently been shown that the genomes of many of the MTV code for superantigens. The predicted amino acid sequences of these superantigens and their specificity for TCR V beta differs for each MTV integrant. This study contains the predicted amino acid sequence and V beta specificity of two MTV superantigens that had not previously been analyzed. The results show that both of these MTV superantigens are specific for TCR that bear V beta 7, but unlike the MTV7 superantigen not for receptors bearing V beta 6 or V beta 8.1. The data also support the conclusion of previous studies that the COOH-terminal sequence of these proteins is a major factor in controlling their V beta reactivity.

Amino Acid Sequence↗
PubMed1992

Inhibition of mouse mammary tumor virus-induced T cell responses in vivo by antibodies to an open reading frame protein.

Minor lymphocyte stimulating (Mls) antigens specifically stimulate T cell responses that are restricted to particular T cell receptor (TCR) beta chain variable domains. The Mls phenotype is genetically controlled by an open reading frame (orf) located in the 3' long terminal repeat of mouse mammary tumor virus (MMTV); however, the mechanism of action of the orf gene product is unknown. Whereas predicted orf amino acid sequences show strong overall homology, the 20-30 COOH-terminal residues are strikingly polymorphic. This polymorphic region correlates with TCR V beta specificity. We have generated monoclonal antibodies to a synthetic peptide encompassing the 19 COOH-terminal amino acid residues of Mtv-7 orf, which encodes the Mls-1a determinant. We show here that these antibodies block Mls responses in vitro and can interfere specifically with thymic clonal deletion of Mls-1a reactive V beta 6+ T cells in neonatal mice. Furthermore, the antibodies can inhibit V beta 6+ T cell responses in vivo to an infectious MMTV that shares orf sequence homology and TCR specificity with Mtv-7. These results confirm the predicted extracellular localization of the orf COOH terminus and imply that the orf proteins of both endogenous and exogenous MMTV interact directly with TCR V beta.

Amino Acid Sequence↗
PubMed1997

T-cell receptor repertoire in matched MART-1 peptide-stimulated peripheral blood lymphocytes and tumor-infiltrating lymphocytes.

Characterization of tumor-associated antigens (TAAs) recognized by CTLs makes the consideration of therapeutic strategies based on peptide stimulation of peripheral blood lymphocytes (PBLs) feasible. Several such approaches are adoptive transfer of peptide-stimulated PBLs, ex vivo peptide stimulation of dendritic cells, and direct vaccination with TAA-derived peptides. A critical component of any of these peptide-based strategies is the requirement that the patient's PBLs are able to react productively against the presented TAA. The purpose of this study, through the study of T-cell receptor (TCR) usage, was to evaluate the T-cell response in matched MART-1(27-35) peptide-stimulated PBLs and tumor-infiltrating lymphocytes (TILs). MART-1(27-35)-reactive PBL and TIL cultures were generated from three patients by in vitro stimulation with an immunodominant peptide of MART-1 (MART-1(27-35)). All cultures had a human leukocyte antigen A2-restricted, MART-1(27-35)-specific CTL response. The TCR usage of each was assessed by the DNA sequence analysis of 50 TCR beta clones obtained by rapid amplification of cDNA ends per culture. TCR analysis suggests a TCR repertoire that differed from patient to patient (8-16 subfamilies were used) and a predominant usage of a different variable beta chain (BV) by each of these MART-reactive T cells. These predominant BV rearrangements were derived from multiple clonotypes because different variable, diversity, and junctional regions were observed. However, a similar pattern of expansion was present for both PBLs and TILs; the relative usage of each prevailing BV was more marked in TILs (36, 50, and 78% of TILs versus 26, 20, and 24% of PBLs, respectively), a broader TCR repertoire was used by PBLs (P > 0.05), and similar TCR subfamily usage was noted when TIL and PBL cultures from the same patient were compared (8 of 11, 7 of 9, and 7 of 8 for patients 1, 2, and 3, respectively). Furthermore, the exact same clonotypes derived from predominant TCR subfamilies in the PBLs and TILs were present in each patient, suggesting peptide-stimulated expansion in both biological compartments. These studies suggest that there will not be a limited and predictable TCR subfamily response to a specific TAA, although reproducible patterns of PBL and TIL expansion are present from patient to patient. Additionally, identical T-cell clonotypes having the same potential for antigen-driven expansion were present in a patient's PBLs and TILs. As such, our data support the conceptualization of approaches using adoptive transfer or vaccination based on TAA-derived peptide stimulation of PBLs.

Amino Acid Sequence↗
PubMed1995

Transfection of TCR alpha-chains into suppressor and T helper cell hybridomas. Production of suppressor factors with predicted antigen specificity.

Conditioned medium from Ag-specific suppressor T cell hybridomas contains soluble factors (TsF) that modulate immune responses in an Ag-specific manner. We previously generated a series of TCR-alpha- and TCR-beta- expression variants from a 4-hydroxy-3-nitrophenyl acetyl (NP)-specific inducer suppressor T cell hybridoma and demonstrated that loss of TCR alpha-chain mRNA, but not TCR-beta chain mRNA, was accompanied by concomitant loss of suppressor bioactivity. Suppressor factor bioactivity was restored by expression of TCR alpha-chain cDNA, suggesting that the TCR alpha-chain plays a critical role in Ag-specific suppressor cell function. We have now transfected TCR alpha-chain from a Th cell clone specific for arsanylated peptides plus I-Ad into a TCR-alpha- derivative of an NP-specific inducer suppressor T cell hybridoma. The transfectants expressed a new hybrid TCR-alpha beta complex and produced soluble factors that suppressed azobenzenearsonate hapten (ABA) but not NP delayed-type hypersensitivity responses. These supernatants mediated suppression of the induction, but not the effector phase of the delayed-type hypersensitivity reaction. In reciprocal experiments we transfected a TCR alpha-chain from an NP-specific suppressor T cell hybridoma into a TCR-alpha- hybridoma derived from the ABA-specific Th cell hybridoma. The NP-specific TCR alpha-chain was expressed in the Th cell hybridoma, but the supernatant from this transfectant did not suppress DTH responses to either NP or ABA. However, the latter supernatants, when combined with cell lysates derived from a TCR-alpha- Ts hybridoma, specifically suppress NP DTH responses. These data are consistent with the interpretation that TCR alpha-chain imparts Ag specificity to the suppressor molecule and a second, yet undefined, component produced by the Ts hybridoma controls the immunoregulatory bioactivity.

Animals↗
PubMed1992

Molecular mimicry by major histocompatibility complex molecules and peptides accounts for some alloresponses.

One explanation offered for the uniquely high precursor frequencies of T cells which recognize allogeneic major histocompatibility complex (MHC) molecules, and their lack of self-MHC restriction, is that the alloreactive cells are polyclonal populations the primary specificity of which is self-MHC plus peptide X1, X2, ... Xn. These are postulated to cross-react with allo-MHC plus peptides Y1, Y2, ... Yn. It has been further suggested that the structural basis for the crossreactivity between different MHC alleles is the similarity in amino acid sequence of that part of the molecule predicted to make contact with the T cell receptor (TcR). In order to test this concept, T cells were obtained with dual specificity for influenza haemagglutinin (HA), restricted by HLA-DR1Dw1, and for DR4Dw4/Dw14 expressed on allogeneic human B cell lines, and the specificity of one clone was studied in detail. The exposed, TcR-contacting surfaces of these two DR molecules are predicted to be identical. Although the HA-specific response was stimulated by DR1-expressing mouse DAP.3 transfectants, DAP.3 cells expressing the alloantigen DR4Dw4 were unable to stimulate, possibly because of a failure to present the necessary human peptide for anti-DR4 allorecognition. Therefore, the effects of pulsing the DR4Dw4-expressing DAP.3 cells with the HA peptide were examined. This peptide is known to bind to both DR1 and DR4. Addition of the HA peptide restored the anti-DR4Dw4 response. These data support the concept that allorecognition in some responder/stimulator combinations can be explained by cross-reactivity at the level of the MHC molecule and the peptide.

Amino Acid Sequence↗
PubMed1997

Use of T cell receptor/HLA-DRB1*04 molecular modeling to predict site-specific interactions for the DR shared epitope associated with rheumatoid arthritis.

OBJECTIVE: To use molecular modeling tools to analyze the potential structural basis for the genetic association of rheumatoid arthritis (RA) with the major histocompatibility complex (MHC) "shared epitope," a set of conserved amino acid residues in the third hypervariable region of the DRbeta chain. METHODS: Homology model building techniques were used to construct molecular models of the arthritis-associated DRB1*0404 molecule and a T cell receptor (TCR) from T cell clone EM025, which is specific for DR4 molecules containing the shared epitope sequence. Interactive graphics techniques were used to orient the TCR on the DR molecule, guided by surface complementarity analysis. RESULTS: The predicted TCR-MHC-peptide complex involved multiple interactions and specificity for the shared epitope. TCR residues CDR1beta D30, CDR2beta N51, and CDR3beta Q97 were positioned to potentially participate in hydrogen bond interactions with the shared epitope DRbeta residues Q70 and R71. CONCLUSION: These results suggest a structural mechanism in which specific TCR recognition and possibly Vbeta selection are directly influenced by the disease-associated MHC polymorphisms.

Amino Acid Sequence↗
PubMedDate not supplied

Mitogens, superantigens, and nominal antigens elicit distinctive patterns of TCRB CDR3 diversity.

The third complementarity-determining region (CDR3) is the only nongermline-encoded hypervariable region of the T cell receptor beta (TCRB) chain, and it is the region that has been predicted to confer fine specificity of the TCR for peptide-MHC complexes. For this reason analysis of TCRB CDR3 heterogeneity may provide insight into immune mechanisms operative in infectious and autoimmune diseases. PBMC stimulated with either mitogen (PHA), superantigen (TSST-1), or nominal antigen (tetanus toxoid) have been compared with unstimulated PBMC using a two-dimensional approach. Analysis of the expressed TCRBV gene repertoire CDR3 length profile coupled with SSCP methodology enabled the discrimination of sequences with the same CDR3 length. For both freshly isolated and PHA stimulated PBMC, a normally distributed spectrum of CDR3 lengths (five or more products) was observed. These products differed by 3 bp (1 amino acid) due to the strict requirement for in-frame rearrangements in the CDR3 region of TCR. By contrast, tetanus toxoid stimulated PBMC had restricted profiles for most TCRBV families after as few as 7 days of incubation. The oligoclonal nature of samples showing CDR3 length restriction was revealed by SSCP analysis and confirmed by sequence determination. Superantigen stimulation resulted in unique patterns of diversity, which included polyclonal expansion of specific TCRBV families as well as oligoclonal expansion of most other TCRBV families. These data reveal complex yet distinct patterns of TCR diversity in response to different T cell activation stimuli.

Adult↗
PubMed1996

Species-dependent post-translational modification and position 2 allelism: effects on streptococcal superantigen SSA structure and V beta specificity.

Epidemiologic and molecular population genetic analyses support a role for superantigens (SAg) in the pathogenesis of severe staphylococcal and streptococcal infections. To investigate how variations in SAg structure influence immunomodulatory activity, we examined the biochemical and functional properties of two allelic variants of streptococcal SAg SSA that differ at position 2. Mass spectrometry revealed both recombinant (Escherichia coli) and native (Streptococcus pyogenes) SSA allelic variants to have significantly larger molecular masses than predicted by primary sequence alone and provided evidence that the proteins were modified by the addition of biochemical moieties, a phenomenon that has not been described for related SAg. Furthermore, the molecular masses of native and recombinant SSA were not the same; SSA was differentially post-translationally modified by the two bacterial genera. The substitution of E. coli-dependent processing for that of S. pyogenes altered both protease digestion and V beta specificity, suggesting that recombinant SAg from E. coli may not accurately represent the native toxin. In addition, the observation that SSA allelic variants differed in V beta specificity supports a role for position 2 in SSA-TCR interactions. That SSA position 2 contributes to V beta specificity could not have been predicted from functional or crystallographic studies of other SAg and suggests that SSA may adopt unique interactions with TCR and/or MHC class II molecules. Determining the structural basis for these differences should offer additional clues to the manner in which SAg exert their effects on the immune system during infection and may allow the designing of SAg mutants with specific quantitative and qualitative immunomodulatory properties.

Alkylation↗
PubMed2005

Diagnostic significance of transferrinuria and albumin-specific dipstick testing in primary care patients with elevated office blood pressure.

This study assesses the diagnostic accuracy of transferrinuria and an albumin-specific dipstick assay for detection of renal target organ damage (microalbuminuria) in hypertensive patients in a general practice setting. A spot urine sample of 130 nondiabetic patients with elevated office blood pressure readings (>140 and/or 90 mmHg) was investigated by measuring albumin to creatinine ratio (ACR) and transferrin to creatinine ratio (TCR) and by using an albumin-specific dipstick test (Micral). ACR was considered as comparative gold standard. TCR was elevated (>0.19 mg/mmol) in 26 urine samples (20.0% of the test samples). ACR was raised in 29 samples (22.3% of the test samples). Elevated TCR had a sensitivity of 97% and specificity of 91% for detection of microalbuminuria. Positive predicting value for microalbuminuria was 65%; negative predicting value was 99%. Correlation between ACR and TCR was strong (r=0.96). Dipstick testing for albumin was positive in 23 urine samples (17.7% of the test samples), 27 (20.8%) tests were false positive and six (4.6%) false negative. When dipstick was positive, the sensitivity of detecting microalbuminuria was 79%, and specificity 73%. In conclusion, detection of urinary transferrin in nondiabetic patients with hypertension is strongly associated with urinary albumin excretion. However, assessment of TCR does not identify additional patients with microalbuminuria compared to measurement of ACR alone. The semiquantitative Micral test offers a simple and valuable method to screen hypertensive patients for microalbuminuria in a primary care setting.

Albuminuria↗
PubMed1998

Estimation of maximal affinities between T-cell receptors and MHC/peptide complexes.

Recognition of peptide/MHC complexes by T-cell receptors (TCRs) is a critical step for T-cell activation. We studied T-cell activation as a function of this interaction using a mathematical model. Unlike other models analysing TCR-MHC/peptide interactions, this study takes into account that both TCRs and MHC/peptide complexes are anchored in membranes and not in solution. The proposed model quantitatively predicts several essential features of antigen-specific T-cell activation, including the experimentally determined rate of TCR-downregulation during peptide-specific T-cell stimulation. In addition, the model offers an explanation as to why the affinity of the TCR for MHC/peptide complexes is low in general and it correctly predicts the on-rates of the TCR-MHC/peptide interaction observed in different model systems. Thus, the proposed model predicts key parameters of T-cell activation and offers an explanation for the surprisingly low affinity of the TCR for its antigen.

Animals↗
PubMed1999

In vitro immunization with a recombinant antigen carrying the HIV-1 RT248-262 determinant inserted at different locations results in altered TCRVB region usage.

Immunodominance or cripticity of a peptide-borne determinant may be influenced by the protein context in which the epitope is embedded. In this frame, we previously showed that certain human T cell clones, derived from different donors, may differentially recognize the RT248-262 helper determinant depending on whether it is provided to the presenting cells as a synthetic peptide or as a recombinant carrier protein to which the sequence of interest is fused. We now report that, upon in vitro immunization of human PBL with autologous APC, the epitope-specific TCRVB repertoire obtained when selection is applied by pulsing the APC with the cognate synthetic peptide is different from that found when a recombinant protein is used in which the antigenic sequence is placed at either a N-terminal or C-terminal location of the GST carrier. As the TCRVB distribution is not a function of the APC used, we propose that processing of different recombinant molecules containing the same epitope may generate MHC/peptide complexes which, being antigenically diverse, may recruit distinct TCR specificities. These findings may be relevant for evaluating and predicting the immunogenic potential of subunit vaccines based on synthetic peptides or on recombinant proteins as compared to the native antigen.

Amino Acid Sequence↗
PubMed1998

A dominant V beta bias in the CTL response after HSV-1 infection is determined by peptide residues predicted to also interact with the TCR beta-chain CDR3.

Many T cell responses are dominated by restricted TCR expression and can range from repeated usage of particular TCR Vbeta- and/or Valpha-elements, to the preferential usage of both V- and J-elements, often in conjunction with conserved V-D-J or V-J junctional sequences. Cytotoxic T lymphocytes specific for a Kb-restricted determinant from the herpes simplex virus glycoprotein B (gB) preferentially express a dominant TCRBV10 beta-chain with sequence conservation of a tryptophan-glycine located in the V-D junction. Here we have examined whether immunisation of C57BL/6 mice with the gB-peptide can mimic the CTL response seen after HSV-1 infection. Immunisation with the gB-peptide resulted in the generation of gB-specific CTL that showed a similar TCRBV10 bias to that observed after HSV-1 infection. When the gB-determinant was expressed as a part of a fusion protein, immunised mice again exhibited the TCRBV10 bias with the junctional sequence conservation in the responding CTL. C57BL/6 mice were then immunised with variants of the gB-peptide that contained amino acid substitutions at positions previously predicted to contact the TCR beta-chain CDR3. Analysis of the TCRBV usage of variant specific CTL lines showed that substitutions at the TCR-contact positions 4, 6 and 7 of the gB-peptide resulted in a loss of the TCRBV10 bias. These results suggest that the TCRBV10 bias seen in gB-specific CTL after HSV-1 infection is due to antigenic selection by the minimal peptide and is determined by residues proposed to contact the TCR beta-chain CDR3.

Amino Acid Sequence↗