Evolution of allorecognition?

letter

Short peplides derived histotompatibility class

I

from human major

complex

(MHC)

HLA

have IXM. $l.ld

molccule5

,;soc~-

ated with most HLA class Ii moleculas

that

have been studied? and are often among the must abundant peptidcs

presenP, Analysis from which these peptides we~dcrived shows a striking pattern Wig. 1). Twenty-one out of 24 HLA of the MHC class I -ions

class

peptkks

I-derived

are derived

I molecule.

class

derived

Only

P,-micrq$obulin surprising

&-m).

was

and two flam

This is sumewbat

since these domains

are all very

in size.

Two trivial explanations explain

probably

do not

First, since the al

this clustering.

and 012 domains

the pa!ymorphic

contain

of the HLA class I molecule,

regions may

of the

one pptide

from the 013 domain,

similar

to cIass II

bound

from the til or 0l2 dmein

be

effectiveiy

more

from than the conserved

chm

quences_

despite

However,

I argenu m-

the

a given

molecule

fr0m

molecules

to

cy3 or &-m

her of possible sequences, can only select

the=

sequences

HLA-DR the class

in the homozygous

present

I

cell

line from which it was derived. Secon& the structure

of the HLA class 1

molecule might f;tvour processing of the regions. However, analysis of the position of these @des within the crystal strutno obvious

ture of HLA class I shows

tern (Fig. II The domain HLA

da55

I and

of these

peptides

peptides suggest5

stnxtures

class It mokules

amongst

self-

is acting to promote &ir prese&tion on HLA class If molecules_ m presmt;itian of self-peptides from the variable region5 of MHC class I molecules

pat-

fadHtak

a&recognition

of the

identical

individuals

are very

elltti

that some form of sekction

peptide

variants

might be a means to Wust:

HLA-DR-

can pelt

different

HLA cla& 1 mokcules. the host in twr, ways_ First, some evidence

and ar2 domains

suggests

of class 1 (Fig. 1X

We propose

important

of HLA class I mol-

rendered

the al

and n2 domains

ccules,

that natuml

presentation

nism of enhancing portance

d

peptides

derived

cculcs grafts

seleckn

of these

has favotired

peptides

as a mecha-

allarecognition.

‘indirect’ from

in the rejection

The im-

(alk~1r~co:ognition of donor

MHC

OF foreign

has been previously

moltissue

describect tre-

viewed in Ref. 3). The over-representation

allarecugnition

might benefit

that maternal-f-1

instead another expkmation for the clustering of these self-p+ide in

in sustaining

Allorecognition

in

recognition

is

getatinn’.

nonral

is of at

least half of their HLA lcwzi:>y mother and HLA

c&s

1 bound

might facilitate DR-identical Sctifld,

peptidr!s derived

from

to da% I[ malccuks

recognition

even in HLA-

maternal-f@:tat

@patphir

HLA

interactions.

MoIetiIes

might

play a role as targets

in the ehmination

pathogens

cel.l-surface

carrying

an&

membrane

pathogens

within

of

cells

fore+

of host

jntraceklar might

be

facilftated by the Gllc-kec~@ticm of forelgn HLA mdecules. Interestingly, it has

most abundant dated

husl-derived bth

with

pmtcins

human

and

assosimian

vaccination

of macaque with SW-infezted DTeven wkkcted humirn cells can produce a (xeno-)response HLA molecules

these ckumstance5

more difficult by the sharing

foetus. Thus variant

cell

Thus, cognition

carrying remnants

immuncdeficimcy viruses WVF. Moreovr?r,

similar but there is no clustering of elukd peptide in the al and 01 domains of class II molecules analogous to that seen in the a3

Enhanced

h-cm-~other ho&.

of vim

hem shown that HLii-DR molecuhz are the

in their

due to variations

derived b&h

of

proteins

prOt=ts

against sumuent

virus derived

ecuk

challenge

a150 off-5

in linkage

with

a rnecbnigm

diwquilibrium

the evolutionary

and thus

maintenance

II n~lecule5

histc
would

the

cell line that

HLA clase I and clans El rnol-

class 1 and cb~

theoq

bwards

from the -ame cell line’.

This proposal that maintains expbin

directed

of the human

of

in a ma)m

complex. C&R test oi this

be

HLA class I-derived

to determine peptides

whether

are abundant

on the cl~s such

II mo1ccuh.x

a5 the mouse

of other species

u-here,

currently,

re-

levant data are lacking’.

book

reviews biology’. Its first section is devoted to the fun-

find some

damentals

allowing

of

amplification,

PCR

even an expert PC&user Such

important

mtitamination strat&es

issue

@imer

from

PCR

Cold

Spring

now

dedicating

polymerase

Harbor

reaction,

viously for moiecular

PCK was first descriW stable polymerase, ampiificaHon ha:

btiome

still &v&ping, complex

repetition

Indeed,

of DNA me&ag,

if - a

primer anneal-

polymerization

-

there are

now dozens of wphisticated

pmtoc~ls

volving

polymerasPs

new

thermostable

with various properties, as modified nucleotides can be applied

in-

and reagents such or primers, which

to an unexpectedly

range of areas 0: ex~fimental

wide

mcarch.

The purpose of this manual is to demonstrate that PCR should be viewed as an ‘alternative

approach

DECEMBER

la standard

molecular

1996

PCR, of PCR-aided

and mutagenesis. numerous

of

innovation

in the ffcld, it 1s also likely that the second

edition of this manual v&tmes

will comprise

much like the ‘MoIecuIar

three

Cloning’

manual!

amplifithe other

different

appli-

on-,

like jm

expression

Library

PCR applications

are so

that not all of them can be pre_

sented in a single manual.

However,

PCR, quantitative

of l?CR and diagnostic

such

aspects

applications

Index

might

more space, probably

at the

expense of s0me very specializ63d pmtc&s.

Your February

isstie of irmmdqy

This new manual displays the same high

to

of PCR is straightforward

ing and DNA

&!l

have deserved it

enon@

several

fication, to more sophtsticated

issues as invem

of iJzvitro

&serve this new contribution. the concept

Since

of the first thcrmo-

Though

already

displacement

is not described),

illustrate

to the continued

use

acid ampIifl-

al-

cloning end cDNA ampli-

of nucleic acids has expanded

exponentia!lp-

strand

of irl vitro nudeic

cation. Owing

applications

(curi-

PCR sequencing,

is

as it did pre-

&hetechnology

the

to some

techndogtes

from classical ones such as

to the

in 1985.

amplification

the power

research

comprehensive

Apart from the 1-t

are dedtited

cations, ranging

Libamtmyh4ir~fd.

the commercia&arnr

ternative

and

powerful a more

analyzed

sections

biology with its now

Cliwifrg:u

famousMdecul17~

sections.

method

matrices

the

prW5

marrual

different

which

ously,

concep-

the

trial,

Laboratory

an entire

chain

to attend

Simpson’s

3ecEturesat OJ.

from Wh

we exterwively

chapters,

cadon

PCR-

optimization

point of views, Template

designing

in subsequent

Iike

and

are described

preparation

l%r those who were unable

will find helpful.

handling

tual and practical

which

standards

as the two others from the same

7ii

will include dw I996 index as

series. The prwtncrrls, some of which have aE rwdy

been published

ual supplemetit

L F&VW in

of PCR

mfims [now included are

the manMetftodsrnd Appli-

in Gcnome Resrmr&),

well-documented

and

clearly

intro-

duced and discussed. There

is little doubt

that this manual

should find its place on the shelve labmatories.

The

clear presentation and

basic

PCR novices

of many wtll get a

of the essential

step-by-step

protocols

cdncepts

to get startrd, while the more experienced should

I

hose

insert

-

comprising the

Subject

Index, Author Inda

Babks

Reviewed Index few all

etrriclcr

publlrhed

&ir year,

and