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PubMed1995

Cross-reaction but no avidity change of the serum antibody response after influenza vaccination.

Pre- and post-vaccination sera from 19 volunteers were analysed by the haemagglutination inhibition (HI) test, virus neutralization (VN) assay and avidity enzyme-linked immunosorbent assay (ELISA). The sera were tested against the three strains in a commercial inactivated influenza vaccine; A/Beijing/353/89(H3N2); A/Taiwan/1/86 (H1N1) and B/Yamagata/16/88. Additionally, a range of earlier strains and one newer isolate were assayed for HI- and VN-antibodies. Large variations in the pre-vaccination HI titres were observed for the viruses tested. However, 8-9 days after vaccination HI titres increased to above the assumed protective level (HI > or = 40) in most subjects. Although a limited number of patients were analysed at each sampling point, the time-profile we observed in this study is consistent with data we have obtained in earlier trials (Cox, R.J. et al., Vaccine 1994, 12,993-999). The VN titres, on the other hand, were low against all influenza strains before and up to 6 days, but increased rapidly 8-9 days after vaccination. A recent H3N2 isolate, A/Beijing/32/92 (H3N2), which had drifted further away from the vaccine strain, reacted to low titres or were negative in both the HI and VN assays. No change in the serum avidity to the influenza surface antigens was detected after vaccination, whereas sera from subjects naturally infected with influenza showed an increase in avidity to the infecting virus strain. The increase in serum avidity observed in the infected subjects is probably due to the increased and prolonged antigenic stimulus provided by the replicating virus.

Adolescent↗
PubMed1987

In vitro measurement of avidity of radioiodinated antibodies.

A determination of the ability of radiolabeled antibodies to bind to their target antigen is an essential step in the initial selection of antibodies for clinical use as well as a quality control measure. In our studies of the 131I-labeled anti-Thy 1.1 antibody treatment of murine lymphoma we have used cell binding assays with a combination of Lineweaver-Burk analysis to determine immunoreactivity and Scatchard analysis to determine antibody avidity. Both assays were systematically influenced by target cell fixation and measurement of avidity was dependent on immunoreactivity. For 131I-labeled anti-Thy 1.1 antibody, avidity was a much more sensitive indicator of iodination damage and predictor of in vivo behavior than was immunoreactivity, while for other antibodies immunoreactivity has been a better indicator of labeling damage. Thus, immunoreactivity and avidity assays are complementary and knowledge of both factors is required for the design of sensitive quality control procedures for radiolabeled antibodies.

Animals↗
PubMed2005

Improvement of cytomegalovirus avidity testing by adjusting the concentration of CMV-specific IgG in test samples.

BACKGROUND: Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection. Primary CMV infection in early pregnancy bears a high risk of fetal damage. Accurate measurement of CMV-specific IgG avidity may help to improve the serodiagnosis of CMV-infected women by determining the time of infection and fetal outcome. OBJECTIVES: To study the performance of the CMV avidity assay with the fully automated Vidas analyzer (bioMérieux) as a function of the concentration of CMV-specific IgG present in the serum sample. STUDY DESIGN: Eighty-two serum samples were investigated from 3 clinical scenarios: 18 individuals with sera negative for CMV-specific IgG and IgM (control group), 20 pregnant women (44 samples) containing CMV-specific IgG- and IgM-antibodies suggesting acute or recent primary infection and 20 patients with evidence of past infection (CMV-IgG positive and CMV-IgM negative). RESULTS: In the group with presumed acute or recent primary infection 12 of 44 sera had CMV-specific IgG values above 100 arbitrary units (AU, bioMérieux)/ml and in these cases an increase in AI was measurable upon dilution of the serum sample. In two cases, AI's were shifted towards or above the cut-off value of AI>or=0.8, indicative of past infection. Dilution of sera which were CMV-specific IgM positive and had specific IgG concentrations of <or=100 AU/ml produced only minor changes in AI. In individuals with serology indicative of past infection, dilution effects similar to the group of acute or recently infected individuals were observed and if CMV-specific IgG was above 100 AU/ml an increase in AI to above or equal to the cut-off could only be calculated after serum dilution. CONCLUSIONS: The results obtained from undiluted patients' sera with high CMV-IgG concentrations indicate that falsely low avidity indices are obtained if these sera are not diluted to below an empirically determined CMV-specific IgG concentration. In addition, the cut-off value for this commercial CMV-IgG avidity assay should be revised.

Antibodies, Viral↗
PubMed2006

Quantitative analysis of HBsAg, IgM anti-HBc and anti-HBc avidity in acute and chronic hepatitis B.

BACKGROUND AND OBJECTIVES: We evaluated hepatitis B virus (HBV) serological markers by novel, quantitative immunoassays in order to study their behaviours and possible role in the various phases of HBV infection. STUDY DESIGN: The quantitative determination of HBsAg and anti-HBc/IgM by chemiluminescent immunoassays (Abbott Architect) and the calculation of anti-HBc avidity index have been carried out on repository specimens from patients with acute or chronic hepatitis B. RESULTS: In acute hepatitis the levels of HBsAg were generally >10,000 UI/mL and decreased sharply in the recovery phase. In 35 anti-HBe-positive chronic hepatitis cases HBsAg levels were generally lower than 10,000 UI/mL (mean: 2655), whereas in five HBeAg-positive chronic hepatitis patients the mean value was 78,756 UI/mL and 90% of specimens exceeded 10,000 UI/mL. The lowest values (mean: 1029 IU/mL) were found in the seven patients with minimal hepatic damage. IgM anti-HBc antibodies were positive in all acute cases and in 68/207 samples (32.85%) from patients with chronic hepatitis, with significantly lower levels (average sample/cutoff (S/CO) ratio: 2.95 in chronic cases versus 25.96 in acute cases; p<0.005). A S/CO value of 10 for anti-HBc IgM had a 100% negative predictive value and a 99.13% positive predictive value for acute hepatitis B. The study of anti-HBc avidity by an experimental procedure showed that an avidity index (AI) threshold of 0.7 had a good efficacy to discriminate the cases of chronic hepatitis, among whom only 2 specimens out of 193 (1.04%) had an AI<0.7. CONCLUSION: The quantitative determination of HBsAg, anti-HBc/IgM and anti-HBc avidity provides additional information and may be useful in the differential diagnosis of acute and chronic HBV infections and in the follow-up of chronically infected patients.

Acute Disease↗
PubMed2006

A novel flow-cytometry-based assay for quantification of affinity and avidity changes of integrins.

Cell adhesion plays an important role in cell-cell contact formation and cell migration. Thus, the assessment of cellular adhesiveness is one important feature when studying cell-mediated immune responses. The interaction of lymphocytes with other cell types such as antigen-presenting cells or vascular-endothelial cells occurs via adhesion molecules including L-selectin, VCAM-1 or ICAM-1. There are principally two mechanisms by which cell adhesion can be enhanced: namely changes in the affinity or avidity of receptor interactions. Conventional plate-based adhesion assays detect both forms. However, they do not permit discrimination between affinity- and avidity-mediated changes in the adhesiveness. Moreover, analysis of cell subpopulations requires cell separation prior to performance of the adhesion assay. Conventional flow-cytometry-based tests make it possible to determine changes in the affinity of integrins at the single cell level. However, they fail to quantify avidity-mediated adhesiveness. Here we describe a novel flow-cytometry-based assay, which allows the detection of both integrin-mediated affinity as well as avidity changes at the single cell level. This opens up the possibility of precisely characterizing the adhesive capacity of subpopulations in heterogeneous cell populations.

Antibody Affinity↗
PubMed2005

Assessment of IgM enzyme immunoassay and IgG avidity assay for distinguishing between primary and secondary immune response to rubella vaccine.

The primary test for the laboratory confirmation of rubella is IgM serology. It is important to distinguish IgM reactivity caused by primary infection from that caused by reinfection or persistence, especially in pregnant women; as termination of pregnancy is considered when primary rubella is diagnosed during the first trimester. In this study, the performance of rubella IgM enzyme immunoassay (IgM-EIA) and rubella IgG avidity assay were compared using well-defined panels of sera from persons vaccinated against rubella and commercial rubella IgM and IgG enzyme immunoassay kits (Dade Behring, Marburg, Germany). The sensitivity and specificity of rubella IgM-EIA were found to be 77.4 and 97.9%, respectively, while the results for rubella IgG avidity assay were 100 and 100%. IgG avidity assay showed higher positive and negative predictive values than the IgM-EIA (100 and 100% compare to 96.9 and 82.9%). In conclusion, the rubella IgG avidity assay is more sensitive and specific than IgM-EIA for differential detection of primary rubella infection from rubella reinfection.

Antibody Affinity↗
PubMed2005

Amount and avidity of serum antibodies against native glycoproteins and denatured virus after repeated influenza whole-virus vaccination.

There is still uncertainty on the correlates of protection by influenza vaccine. To determine the relationship between hemagglutination-inhibition (HI) titer and the specificity and avidity of serum antibodies, we analyzed serum from a longitudinal trial (1983-1987) of influenza vaccine efficacy [Keitel WA, Cate TR, Couch RB, Huggins LL, Hess KR. Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five year period. Vaccine 1997;15(10):1114-22 ]. We captured native virus particles with fetuin and separately measured relative antibody levels and avidities of antibodies against native glycoproteins and antibodies against denatured viral proteins. Most subjects had pre-existing antibodies against A/Victoria/75 and, although 70% had >two-fold increased antibodies against A/Philippines/82 after vaccination, only 30% showed increased antibodies to A/Victoria/75 indicating no dominance of original antigenic sin. There was variation in the levels of antibodies to unfolded antigens compared to native, but antibodies against denatured proteins never exceeded those against native virus. In some cases, the avidity increased without a significant increase in antibody concentration, which might explain why some vaccinees with low HI titer demonstrate adequate protection. We found that the negative correlation between pre-vaccination HI titer and the increase after vaccination is also seen when antibodies are measured directly, but that there is little relationship between HI titer and antibodies against native glycoproteins, either in amount or avidity. Our assay, which has also been adapted for recent influenza viruses that do not bind to fetuin, may be useful for vaccine evaluation.

Adult↗
PubMed2005

Detection of secondary mumps vaccine failure by means of avidity testing for specific immunoglobulin G.

The aim of this study was to discriminate between primary and secondary vaccine failure in children with mumps using IgG avidity testing. Thirty-nine serum samples from children with mumps, confirmed by specific IgM, were studied. The patients were grouped according to their immunization status. The secondary immune response was defined by IgG with an avidity index >32%. A secondary response in infected children previously immunized was considered as a secondary vaccine failure. Vaccinated children presented higher IgG titers and IgG avidity than unvaccinated children. The proportion of secondary immune responses in unvaccinated patients was lower than that obtained in previously vaccinated infected patients. Avidity testing can be a useful tool to detect secondary vaccine failure in mumps.

Antibodies, Viral↗
PubMed1997

Comparison of clinical characteristics and frequency of implantable defibrillator use between randomized patients in the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial and nonrandomized registry patients.

In the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial, all patients who meet the study entry criteria are followed in a registry. During the period between June 1993 and June 1995, of 1,117 patients who were enrolled in the registry and met the study entry criteria, 476 were randomized to receive either implantable cardioverter-defibrillators (ICDs) or drug therapy (amiodarone or sotalol), and 641 patients were not randomized for a variety of reasons including: patient refusal (42%); physician refusal (43%); concerns about ability to maintain follow-up over several years (10%), and others (6%). There were no significant differences between the 476 randomized and 641 nonrandomized patients with regard to clinical characteristics, left ventricular function, history of congestive heart failure, medical history, and previous cardiac procedures performed before the index event, except that randomized patients were slightly older (65 vs 62 years) and had a slightly higher prevalence of coronary artery disease and previous myocardial infarction. The index event and location of the index event were not significantly different between the 2 groups. Although 14% of registry patients received neither ICD nor antiarrhythmic drug therapy, ICDs were no more frequently used in the registry patient than antiarrhythmic drugs (45% for ICD vs 42% for drugs). Thus, randomized AVID patients have very similar clinical characteristics, cardiac history, and presenting arrhythmias as to nonrandomized eligible patients. Therefore, the results of the AVID trial may be generalized for all patients with AVID-eligible arrhythmias.

Adolescent↗
PubMed1999

Thyroid antibody titer and avidity in patients with recurrent miscarriage.

OBJECTIVE: To determine whether the titer and avidity of the thyroid peroxidase antibody differs between pregnant women in their first trimester who have a history of recurrent miscarriage and whose pregnancies continue to term and those whose pregnancies fail again later in the first trimester. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Pregnant women in their first trimester who had a history of recurrent miscarriage (> or = 3 miscarriages) and who were known to be positive for the thyroid peroxidase antibody. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Thyroid peroxidase antibody titer and avidity (i.e., the net binding strength between antibody and antigen). RESULT(S): At the time of presentation, thyroid peroxidase antibody titer and avidity was significantly higher in those women who later miscarried compared with those whose pregnancies continued. In those whose pregnancies continued to term, titer and avidity declined as the pregnancy progressed. CONCLUSION(S): Autoimmunity plays a role in recurrent miscarriage. Among a group of patients who had had recurrent miscarriages, there appeared to be differences in the humoral response to the pregnancy between those whose pregnancies continued to term and those whose pregnancies failed again.

Abortion, Habitual↗
PubMed2003

Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus.

Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined.

Amino Acid Sequence↗
PubMed2002

Avidity maturation following vaccination with a meningococcal recombinant hexavalent PorA OMV vaccine in UK infants.

To date, there are no data assessing the utility of avidity indices as a surrogate marker for the induction of immunological memory following meningococcal serogroup B outer membrane vesicle (OMV) vaccination. We studied infants who had been immunized with three doses of a recombinant hexavalent PorA OMV vaccine at ages 2-4 months, together with a fourth dose at age 12-18 months. A control group had received a single dose of the same vaccine at age 12-18 months. As previously reported, serum bactericidal antibody (SBA) titres increased after each of the first three doses, with a significant increase observed from 6 months post third dose to 1 month post fourth dose. The geometric mean avidity indices (GMAI), against strain H44/76 OMVs, increased from 1 month post first dose to 1 month post third dose. Significant increases in GMAI were observed at 6 months post third dose and again following the fourth dose. At 32-42 months of age, though the SBA titres had returned to post first dose levels, the GMAI remained elevated. No increase in avidity was observed in the control group. Antibody avidity indices are useful laboratory markers for the priming of immunological memory following vaccination with meningococcal serogroup B OMV vaccines.

Antibodies, Bacterial↗
PubMed1999

Causes of death in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.

OBJECTIVES: This study analyzed the causes of death in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. BACKGROUND: Both implantable cardioverter-defibrillators (ICDs) and antiarrhythmic drugs (AADs) are used as mainstays of treatment for life-threatening ventricular arrhythmias in patients who have survived either ventricular fibrillation or sustained ventricular tachycardia with hemodynamic compromise and serious symptoms. The AVID Trial compared the effectiveness of these two therapies. Survival was better with the ICD. Assessment of the cause of death should help to determine the mechanism of improvement in survival with the ICD. METHODS: Of 1,016 patients enrolled in the AVID Trial, 202 patients died. The mode of death was determined by the unblinded Principal Investigator and independently by an Events Committee, which reviewed materials meticulously blinded with respect to treatment. Deaths were classified as cardiac or noncardiac. Cardiac deaths were further classified as arrhythmic or nonarrhythmic, and causes of noncardiac death were identified. RESULTS: Deaths were more frequent in patients treated with an AAD (n = 122), compared with patients treated with the ICD (n = 80), unadjusted p < 0.001, p = 0.012 adjusted for sequential monitoring. In AVID, 157 deaths were cardiac, and 79 were arrhythmic. The major effect of the ICD was to prevent arrhythmic death (AAD = 55, ICD = 24, nominal unadjusted p < 0.001). Nonarrhythmic cardiac deaths were equal (AAD = 39, ICD = 39). Patients treated with an AAD had a slightly greater incidence of noncardiac deaths (28 vs. 17, p = 0.053), primarily due to pulmonary and renal causes. CONCLUSIONS: The ICD is more effective than an AAD in reducing arrhythmic cardiac death, while nonarrhythmic cardiac death is unchanged. Of note, apparent arrhythmic death still seems to constitute 38% of all cardiac deaths despite treatment with an ICD. However, the ICD remains superior to an AAD in prolonging survival after life-threatening arrhythmias.

Aged↗
PubMed1998

Comparative evaluation of the use of immunoblots and of IgG avidity assays as confirmatory tests for the diagnosis of acute EBV infections.

BACKGROUND: Despite the availability of several different markers for Epstein--Barr virus (EBV) serology, the EBV status of some patients cannot be resolved from a single serum sample with routine testing. To avoid the requirement of follow-up samples, supplementary tests have to be used in these cases. OBJECTIVE: To evaluate the usefulness of avidity and immunoblot assays as supplementary tests for the diagnosis of acute EBV infections. STUDY DESIGN: Three groups of samples for which a definite diagnosis on the EBV status could not be obtained with the routine serological tests were further examined by an EBV IgG avidity assay, by an immunoblot based on a lysate of EBV infected cells, and by a second immunoblot based on recombinant EBV antigens. The three groups consisted of 38 samples with negative/borderline EB nuclear antigen 1 (EBNA-1) antibodies, negative/borderline EBV IgM and positive EBV IgG; 10 samples with indeterminate EBNA-1 and/or EBV IgM assays because of control antigen reactions; and 4 samples with positive EBV IgM results that were not plausible. RESULTS: The avidity assay differentiated between acute and past infections for all samples. In contrast, some cases remained unresolved with both the recombinant and the lysate immunoblot. Two samples were incorrectly classified with the lysate immunoblot. Interpretation of the lysate immunoblot banding patterns was complicated when anticellular antibodies were present. CONCLUSION: Avidity testing appears to be the confirmatory method of choice to differentiate between acute and past EBV infections.

Acute Disease↗
PubMed2001

Maturation of IgG avidity to individual rubella virus structural proteins.

BACKGROUND: the structural proteins of rubella virus, the capsid protein C and the envelope glycoproteins E1 and E2 were produced in lepidopteran insect cells using baculovirus expression vectors. The C-terminal ends of the corresponding proteins were fused to a polyhistidine tag for easy and gentle purification by metal ion affinity chromatography. OBJECTIVES: to investigate the maturation of natural and vaccinal IgG avidity against individual authentic and recombinant rubella virus (RV) structural proteins. STUDY DESIGN: the analysis was carried out using a modified immunoblotting technique where the purified baculovirus-expressed proteins were compared with authentic rubella virus proteins. Altogether, 47 well-characterised serum samples from both naturally infected patients and vaccines were studied. RESULTS: after natural RV infection, IgG antibodies specific for the E1 protein were predominant not only in terms of levels, but also in terms of rate and magnitude of avidity maturation. The avidity development of the IgG antibodies was much slower in vaccines than in patients after a natural RV infection. CONCLUSIONS: together, our results indicate that IgG avidity determination in conjunction with immunoblot analysis is useful in the diagnosis of a RV infection. The recombinant proteins showed similar reactivity patterns in the immunoblot analyses as compared with the authentic viral structural proteins, suggesting suitability for serodiagnostics.

Antibodies, Viral↗
PubMed2000

Secondary measles vaccine failures identified by measurement of IgG avidity: high occurrence among teenagers vaccinated at a young age.

Failure to seroconvert (primary vaccine failure) is believed to be the principal reason (approx. > 95%) why some vaccinees remain susceptible to measles and is often attributed to the persistence of maternal antibodies in children vaccinated at a young age. Avidity testing is able to separate primary from secondary vaccine failures (waning and/or incomplete immunity), but has not been utilized in measles epidemiology. Low-avidity (LA) and high-avidity (HA) virus-specific IgG antibodies indicate primary and secondary failure, respectively. Measles vaccine failures (n = 142; mean age 10.1 years, range 2-22 years) from an outbreak in 1988-9 in Finland were tested for measles-virus IgG avidity using a protein denaturating EIA. Severity of measles was recorded in 89 failures and 169 non-vaccinees (mean age 16.2 years, range 2-22 years). The patients with HA antibodies (n = 28) tended to have clinically mild measles and rapid IgG response. Among failures vaccinated at < 12, 12-15 and > 15 months of age with single doses of Schwarz-strain vaccine in the 1970s, 50 (95% CI 1-99), 36 (CI 16-56) and 25% (CI 8-42) had HA antibodies, respectively. When a single measles, mumps and rubella (MMR) vaccine had been given after 1982 at 15 months of age, only 7% (CI 0-14) showed HA antibodies. Omitting re-vaccinees and those vaccinated at < 15 months, Schwarz-strain recipients had 3.6 (CI 1.1-11.5) higher occurrence of HA responses compared to MMR recipients. Apart from one municipality, where even re-vaccinees had high risk of primary infection, 89% (CI 69 to approximately 100) of the infected re-vaccinees had an HA response. Secondary measles-vaccine failures are more common than was more previously thought, particularly among individuals vaccinated in early life, long ago, and among re-vaccinees. Waning immunity even among individuals vaccinated after 15 months of age, without the boosting effect of natural infections should be considered a relevant possibility in future planning of vaccination against measles.

Adolescent↗
PubMed2000

Progression of autoimmune diabetes driven by avidity maturation of a T-cell population.

For unknown reasons, autoimmune diseases such as type 1 diabetes develop after prolonged periods of inflammation of mononuclear cells in target tissues. Here we show that progression of pancreatic islet inflammation to overt diabetes in nonobese diabetic (NOD) mice is driven by the 'avidity maturation' of a prevailing, pancreatic beta-cell-specific T-lymphocyte population carrying the CD8 antigen. This T-lymphocyte population recognizes two related peptides (NRP and NRP-A7) in the context of H-2Kd class I molecules of the major histocompatibility complex (MHC). As pre-diabetic NOD mice age, their islet-associated CD8+ T lymphocytes contain increasing numbers of NRP-A7-reactive cells, and these cells bind NRP-A7/H-2Kd tetramers with increased specificity, increased avidity and longer half-lives. Repeated treatment of pre-diabetic NOD mice with soluble NRP-A7 peptide blunts the avidity maturation of the NRP-A7-reactive CD8+ T-cell population by selectively deleting those clonotypes expressing T-cell receptors with the highest affinity and lowest dissociation rates for peptide-MHC binding. This inhibits the local production of T cells that are cytotoxic to beta cells, and halts the progression from severe insulitis to diabetes. We conclude that avidity maturation of pathogenic T-cell populations may be the key event in the progression of benign inflammation to overt disease in autoimmunity.

Animals↗
PubMed1992

Restimulated memory Tc cells have a higher apparent avidity of interaction with targets than primary virus-immune Tc cells as indicated by anti-CD8 blocking.

Previous experiments have shown that whereas a secondary in vitro Kunjin-immune cytotoxic T (Tc) cell population lysed equally well targets infected with either native flavivirus or a recombinant vaccinia virus expressing the immunodominant determinant, primary in vivo Kunjin-immune Tc cells were able to lyse only the recombinant vaccinia virus-infected targets. Using CD8 blockade to assess the avidity of T cell-target interaction, recombinant-infected targets express antigen more efficiently than native flavivirus infected targets and secondary in vitro Kunjin-immune Tc cells have a higher avidity for targets than do primary in vivo Kunjin-immune Tc cells. Secondary in vivo influenza-immune Tc cells are also of higher avidity than primary in vivo influenza-immune Tc cells. Thus, a restimulated memory Tc cell population interacts with targets with greater avidity than does a recently activated naive population.

Animals↗